Seven men and one woman with primary affective disorder, mania, were given a slow intravenous infusion of physostigmine salicylate. In six patients, mood and thought content changed from mania toward depression as evaluated by either a visual analog mood scale or the Pettersen scale. Two other patients, who were the only predominantly irritable manics in the study, demonstrated little change in their hostility, although one became somewhat depressed. These findings are consistent with earlier reports of suppression of manic symptoms after physostigmine infusion in some but not all patients with mania. The pharmacologic mechanism of physostigmine reversal of manic symptoms may be the direct result of increased cholinergic activity or a result of the effect of increased cholinergic activity on other brain neurotransmitters.