The present study evaluated the safety of and obtained preliminary data on the cognitive effects of l-deprenyl and physostigmine in patients with Alzheimer's Disease. Seventeen outpatients with Alzheimer's Disease participated in a double-blind crossover study in which they received 4 weeks of l-deprenyl at a dose of 10 mg p.o., q.d., and 4 weeks of placebo in random order. During both the l-deprenyl and placebo periods, patients received cognitive assessments during physostigmine (0.5 mg) and placebo infusions separated by 2 days. The cognitive effects of these agents alone and in combination were measured with digit span, verbal fluency, list learning, praxis, delayed recall, and delayed recognition tasks. Fifteen patients completed the study. The two drugs, used alone or in combination, were safe and well tolerated. Analyses of variance demonstrated that neither physostigmine nor l-deprenyl, whether given alone or in combination, significantly improved cognition, when compared with the double placebo condition.