In a double-blind, placebo-controlled, crossover study of intravenously administered naloxone hydrochloride, 54 subjects with clinically ascertained Alzheimer's disease tested at three university centers showed no significant improvement in neuropsychological performance after 1-mg or 10-mg doses; 15 patients at 1 center were similarly unimproved after receiving 30 mg naloxone (single blind). Findings fail to support claims that naloxone monotherapy ameliorates cognitive impairments of Alzheimer's disease.