Two hundred eighty-one patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were enrolled in a double-blind, placebo-controlled trial of the efficacy and safety of orally administered zidovudine (azidothymidine or AZT). Significant clinical benefits and adverse experiences have been reported from this trial. Because neuropsychiatric dysfunction is often associated with human immunodeficiency virus (HIV) infection, a brief affective and neuropsychological examination was administered over 16 weeks of the trial to evaluate any changes in neuropsychological function that occurred with drug administration. Patients receiving zidovudine, particularly those with AIDS, showed improved cognition as compared with patients receiving placebo. There were no changes in affective symptoms. The zidovudine recipients also had a statistically significant reduction in the intensity of symptomatic distress during the trial that may account in part for the observed cognitive changes. Some improvement in various cognitive measures was also seen in patients with AIDS-related complex. The results of this study suggest HIV-associated cognitive abnormalities may be partially ameliorated after the administration of zidovudine.