The cognitive-enhancing effects of pramiracetam in animal models of learning and memory are characterized by an inverted U-shaped dose-response curve. We evaluated antidementia efficacy of this drug in 10 patients with probable Alzheimer's disease employing a 2-phase, placebo-controlled, enrichment-type trial design. Eight patients evidenced a best dose in the dose-finding phase, but in the subsequent replication phase only two again improved to a similar degree. PETs with fluorodeoxyglucose obtained in two individuals showed no definite change. Doses up to 4,000 mg pramiracetam are unlikely to confer symptomatic benefit to Alzheimer's disease patients.