The authors evaluated the cognitive effects of acute challenges with the H2receptor-antagonist cimetidine in normal older volunteers. The study was a double-blind, placebo-controlled, crossover study of 12 volunteers, average age 71.25 years. Baseline assessment was followed by randomized administration of a placebo or ascending doses of cimetidine (400 mg, 800 mg, or 1,600 mg) in test sessions separated by 1 week. Cognitive performance was evaluated with a 1-hour battery of tests beginning 90 minutes after administration of a single dose of drug (or placebo). There were no significant cognitive decrements associated with cimetidine. Despite numerous case reports of cognitive toxicity, this study found no observable decrements in cognitive performance in a group of healthy elderly subjects; therefore, case reports in the literature may be reporting effects for patients with specific impairments or sensitivities.