|For the Agents of S.H.I.E.L.D. version of Madame Hydra, see Aida.|
- "Attention all security staff, this is Madame Hydra! It seems my little pets are escaping their pens. All long-range units converge on the eastern rail bridge. The rest of you... KILL THE SUPER SOLDIER!"
- ―Madame Hydra
Following Captain America's defeat of Baron Wolfgang von Strucker, he was ambushed and captured by the mechanical Iron Cross and taken to the dungeon complex beneath Castle Zemo. While he was blacked out, Zola took a sample of Rogers' blood to recreate the Super Soldier Serum, before leaving the Captain himself in the custody of the new Warden of the dungeons - Madame Hydra. Hydra roughly abused Rogers, though Zola made it explicit that she was not to kill him yet, and after she restrained him she took the time to mockingly reveal that she had kidnapped his friends James Montgomery Falsworth, Bucky Barnes and Dum Dum Dugan of the Howling Commandos and that Zola did not object if she broke them. Breaking free of the restraints and escaping his cell, Rogers rescued Bucky and prepared a massive prison riot, infuriating Madame Hydra and freeing the POWs who served as her "test subjects". Once Bucky escaped Castle Zola with a train loaded with the POWs, Rogers went to rescue Dugan, but Zola's Screamers escaped their confinement and Madame Hydra ordered her troops to leave Dugan behind as bait while she escaped with Falsworth. Rogers fought his way through the Screamers and rescued Dugan, at which point the two split up with Roger pursuing Hydra before she could kill or do something even worse to Falsworth. Rogers found Hydra holding Falsworth prisoner and Dugan shot down her bodyguards, forcing her to retreat inside.
Pursuing Madame Hydra across the castle, Rogers eventually cornered her in Zemo's Ballroom. She used smoke bombs to disguise her reinforcements from Rogers, and fired at him with her custom machine pistols from a ledge far away from him. However, Rogers managed to defeat her reinforcements and use his vibranium shield to deflect the bullets back at her, forcing her to flee. Rogers caught her and the two fought hand to hand, where he proved to be superior - before finally deflecting her bullets past her, triggering a massive explosion behind her. The blast horribly scarred half her face, but she declined Rogers' offer to get her the medical help she needed, claiming her scars were a badge of honor and escaping on an aircraft outside. While she escaped Castle Zemo, her final words with the Captain revealed that her Commander, the Red Skull, would be on his way to the castle soon. While her fate after the battle is currently unknown, the consequences of her actions continued to haunt Rogers for the rest of his mission in Castle Zemo - and almost leading to Falsworth being transformed into a mind-controlled super soldier to use as an assassin for the nefarious purposes of Zola.
Madame Hydra had Arnim Zola use the reality-warping powers of the Tesseract to shrink down a pair of fully-automatic high powered rifles to the size of mere pistols, creating a pair of custom devastating Machine Pistols. Like the process that crafted Wolfgang von Strucker's Satan Claw, the pistols proved too costly to effectively mass-produce, but Hydra's skill and lethality wielding them easily made a single set of them worth it, in Zola's mind.
Alongside her Machine Pistols, Hydra used an arsenal of deadly poisons, many of which were fine-tuned on the vast number of allied prisoners of war stored in the dungeons of Castle Zemo. Her affinity for poisons was so great, that she developed a special toxic venom to replace her own saliva. In addition, she used a number of poison-gas grenades in her battle with Captain America, both to block out his vision of her reinforcements and to damage him in an attempt to retreat.
- HYDRA - Allies
- Heinrich Zemo - Unwilling Ally
- Omega - Subordinate
- Invaders - Former Captives
- In the comics, Madame Hydra is a title used by several HYDRA operatives, the most notable being Ophelia Sarkissian who was a student of Daniel Whitehall and the lover of the Red Skull.
- Another version of the character appeared in 20th Century Fox's production The Wolverine, as one of the antagonists. She is portrayed by Svetlana Khodchenkova. That version is known as "Viper" instead of "Madame Hydra", goes by the alias Dr. Green, and is a mutant instead of a genetically-altered human.