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The sixth and final quest of this Act can be activated if you talk to Ormus after entering Travincal:

Ormus
Diablo and Baal have surely found the Temple City by now. They seek to free their brother, Mephisto, who was imprisoned by the Horadrim in the Temple's Guardian Tower. You must reach him before his Brothers do and prevent them from releasing Hatred upon the world.
DII Icon The Guardian.png The Guardian
Smash the Compelling Orb with Khalim's Will to open the way to Mephisto's Durance.

If you talk to anyone before leaving, some responses may differ if you haven't returned Lam Esen's Tome to Alkor:

Ormus Asheara
Make haste! Though the Three are sure to reunite, it is uncertain as to what they have planned once they do.

Be cautious, my friend. Though you are mighty, no mortal can stand alone against the power of the Prime Evils.
I sent a few of my Iron Wolves on a scouting mission into the jungle near the Temple City... They encountered two cloaked men who attacked them with horrifying powers.

My men barely survived. I have to assume that the two strangers are Diablo and Baal.

You'd better hurry. They're close to finding their brother.
Natalya
Now you rush to face Mephisto. Don't give in to your hatred. That is his greatest weapon against you.
Deckard Cain Hratli Lam Esen's Tome quest completed
The Ancient Horadrim always feared that the Three would escape their prisons and unite. I can't believe that I, the last of their Order, have seen it come to pass.

You are the only one who can prevent this, my friend. The final hour draws near.
Mephisto, along with Baal, was originally captured in the desert near Lut Gholein. But imprisoning two of the Brothers together was far too dangerous.

The Horadrim built the Guardian Tower to hold Mephisto. When Zakarum came to power in this land, it took over the Temple City without paying any heed to what was locked within the Tower.

And it became their doom.
Deckard Cain Lam Esen's Tome quest completed Hratli
You must reach Mephisto before his brothers do. I hear there is a little family reunion about to take place in Kurast. The Three brothers draw close.
Alkor Alkor Lam Esen's Tome quest completed
We have seen Diablo, but remain unsure of his Brothers' whereabouts. The hidden ways of the Tower are long forgotten. Though... it is rumored to have been built as far below the ground as above it.
Meshif Meshif Lam Esen's Tome quest completed
Move quickly, my friend, and end this curse once and for all! Be careful when you return to the Tower. Though many of the followers of Zakarum have fled, there's no telling what horrors still lurk inside it.

If you haven't already done so, and you can't use another player's portal to enter the Durance of Hate after killing the High Council in the Blackened Temple of Travincal, now is the time to complete Khalim's Will, using it to destroy the Compelling Orb: once you've done so, and killed the three members of the High Council, even Champion and Unique Zakarum Zealots will flee from you throughout Kurast. Meanwhile, after destroying the Orb, the stair opposite the Temple's entrance opens to the Durance of Hate below...

Durance of Hate Level 1

Entering the first level of the Durance of Hate activates this quest if talking to Ormus has not already done so:

DII Icon The Guardian.png The Guardian
Search for Mephisto in his Durance.

If you return before killing Mephisto on the third level of his Durance, some responses may differ if you haven't returned Lam Esen's Tome to Alkor:

Ormus Ormus Lam Esen's Tome quest completed
I am loath to describe what will happen if Diablo and Baal release Mephisto. I understand that the great Patriarch of Zakarum, Sankekur, now embodies Mephisto.

You must overcome Hatred lest Terror and Destruction claim us all!
Deckard Cain
Search the Tower thoroughly. Mephisto must not escape.
Alkor Alkor Lam Esen's Tome quest completed
I'm afraid both fear and a large dose of elixir preclude me from answering. Well, the good news is that events are unfolding just as Lam Esen foretold. The bad news is that the story ends in our utter ruin!
Hratli Hratli Lam Esen's Tome quest completed
Shouldn't you be running frantically up and down stairs about now? Why build a Tower to place the beast below ground? At times I believe the Horadrim lacked common sense.
Asheara Asheara Lam Esen's Tome quest completed
We will fight to the death. The sudden reduction in our ranks makes us eager to destroy Diablo and his brothers. Vengeance for the Iron Wolves!
Natalya Meshif
Beware, my friend. Sankekur may be the most powerful mortal in the world. He controls thousands of fanatical worshippers and embodies the Lord of Hatred, himself. His death will be no easy task. I ought to return to the ship. We may have to sail from here very quickly.

The first level is randomly populated by three of the following four monster types: Cadavers, Dark Lords, Maulers and Undead Stygian Dolls (so there's 25% chance of being populated exclusively by undead). The most direct route to the second level is most likely to be found by traveling left after entry.

Durance of Hate Level 2

The second level is similarly populated to the first. The most direct route to its waypoint is most likely to be found by traveling left after entry; continue to do so for the most likely direct route from the waypoint to the third level. This is particularly important to remember in Nightmare and Hell, since the level becomes much larger.

Durance of Hate Level 3

DII Icon The Guardian.png The Guardian
Kill Mephisto.

The third and final level is randomly populated by Blood Lords, with Champion and Unique Undead Stygian Dolls in Normal as well. The approach to Mephisto himself is guarded by the three remaining members of the High Council.

The layout of this level is always the same: you enter at the northeast end of a hall along the southeast end of it, with a doorway in the middle of its northwest wall, through which is the foot of the large chamber containing Mephisto at its head. Clear the hall before approaching this doorway...

Bremm Sparkfist

Super Unique Council Member (Aura Enchanted Lightning Enchanted)

Bremm Sparkfist and his minions guard the foot of Mephisto's chamber, either close to its entrance or, hopefully, to the north, where they're unlikely to become aware of you as you enter if you turn left. It can potentially get quite nasty if they're close to the door and Champion and Unique monsters are also to its left: be prepared to retreat at the first sign of trouble (usually a summoned Hydra before you even enter).

Once you've avoided or killed Bremm, you'll find that there's a lake of blood in the middle of the chamber, shaped like a human body: you're at its foot, with a walkway between the legs opposite the entrance that ends before it reaches the Infernal Gate at the heart of the lake. You won't be able to go through this portal to Hell until you've killed Mephisto.

There are also walkways around the perimeter of the lake to the left and right, but its arms extend to create a moat separating you from its northwestern shore: you can go through a room to either side to reach it, or Leap or Teleport across. However, each flank is guarded by one of the last remaining members of the High Council...

Maffer Dragonhand

Super Unique Council Member (Extra Strong Extra Fast)

Maffer Dragonhand guards the left flank, to the southwest of the lake. Although he's normally more dangerous than Wyand Voidbringer, neither has any minions and if Bremm Sparkfist and his minions spawned far enough away from the doorway to allow you to sneak past, then the left flank may still be preferable.

Wyand Voidbringer

Super Unique Council Member (Mana Burn Teleportation)

Wyand Voidbringer guards the right flank, to the northeast of the lake, without minions.

Mephisto

Evil

My brothers have escaped you!

You're too late!

Once you've crossed the moat to its northwestern shore, Mephisto can be found at the head of the lake. When he attacks, you shouldn't advance any further to the northwest, because although there's a chest there, there can also be other monsters present as well.

Mephisto's most potent attack is a missile which inflicts both physical and cold damage (and length), so even ranged attackers and casters may want to move into melee range to reduce its frequency, or be prepared to dodge: the moat can be used to separate you from Mephisto so that you can maintain distance. He can also emit charged bolts and a poison cloud at closer range, but these are less dangerous if properly resisted.

Once Mephisto is killed, among other things he drops Mephisto's Soulstone, requiring one inventory space. If you don't pick this up, Deckard Cain does so for you so that it can be destroyed on Hell's Forge.

DII Icon The Guardian.png The Guardian
Quest completed.
DII Icon The Guardian.png The Guardian
You completed this quest in a previous game.

If you approach the Infernal Gate from this side after killing Mephisto, a bridge of bones will now rise out of the blood to allow you to go through it. If you return to the Kurast Docks, Natalya will be gone but you can still talk to anyone else:

Ormus Deckard Cain
You have defeated a Prime Evil in combat. Ormus is impressed beyond words. But staying here will not end this conflict.

You must enter the Infernal Gate and stop Diablo once and for all.
Our faith in you was well deserved. But Diablo has made his way to Hell; and it is likely that Baal followed him there.

Enter the Infernal Gate and kill the Lord of Terror before all is lost. Only then will our world be saved!
Alkor Hratli
Your news is great indeed. You have saved us all. I would smile, but I'm afraid my face might collapse. It looks like you're going to Hell before me.

Put in a good word.
Asheara Meshif
Well done, my friend. You are a great champion of Order. Please, consider yourself an honorary Iron Wolf. Ahh... Now, Kurast can begin the task of rekindling its former glory... I thank you.