MacGregor's Syndrome was the disease which filled up the lungs with fluid and made it very hard to breathe. There were four stages of infection, with Nora Fries, the wife of Victor Fries, who suffered from Stage Four of that illness, with Victor placing her in cryogenic stasis so that he could find a cure for it. During his research, Fries fell into some of the liquid chemicals that were used for the stasis process and was mutated into his new form of 'Mr. Freeze', but continued his research into MacGregor's Syndrome.

In the course of his confrontation with Freeze, Bruce Wayne learned that Alfred Pennyworth also suffered from MacGregor's Syndrome. When Batman discovered Fries's Lab and the suspended body of Nora, the analysis of the doctor-turned-criminal's notes revealed that he had found a cure for Stage One of the disease and made good progress on a cure for Stage Two; while Freeze was still far from ready to cure Nora's Stage Four MacGregor's Syndrome, he had already surpassed all other work on that disease.

Freeze was briefly manipulated by Poison Ivy into believing that Batman had killed Nora by deactivating her life-support systems, which drove him to agree to Ivy's plan to wipe out all human life to vent his rage against Batman and the society that created him. However, once Freeze's plan was defeated and Ivy was incapacitated, Batman revealed that Nora was still alive and he never killed her. After he appealed to Dr. Victor Fries, Batman asked his 'foe' to show true power by giving life rather than taking it and sharing the cure for Stage One of MacGregor's Syndrome. After he was moved by Batman's appeal to the man that he had once been, Freeze provided him with two vials of the cure, which restored Alfred to full health by the following morning. In return, Batman ensured that Nora would be moved to the Arkham Asylum Labs so that Freeze could continue his research into the disease.

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