Shy neurologist Malcolm Sayer (Robin Williams) is assigned to work with a group of catatonic patients who, ever since an epidemic of encephalitis ("sleeping sickness") decades before, have not spoken or appeared to understand anything that was going on around them. Everyone else has given up hope, but Sayer notices they have reflex reactions and believes that new medication for Parkinson's disease may help. His superiors object, but he gets permission to try it on one patient, Leonard Lowe (Robert De Niro). At first, there is no reaction, but soon Leonard "awakens." His transformation is so thrilling that Malcolm is easily able to get permission and funding to treat the other patients, and the results are amazing. But eventually, Leonard becomes hyperactive, angry, and ridden with tics. The medication's side effects begin to overwhelm him. Malcolm sees that he is losing Leonard, and the other patients know that it must soon happen to them, too.