Anxiety is a prominent feature of human immunodeficiency virus (HIV)-related psychiatric disorders. Psychiatric disorders are associated with poor drug abuse treatment outcome in both healthy and HIV-infected drug users. While it is important to treat anxiety, the use of traditional antianxiety agents such as benzodiazepines can lead to adverse effects such as sedation and misuse, especially in patients with drug abuse problems. A retrospective chart review was employed to examine the use of buspirone in treating anxiety in intravenous drug users with acquired immune deficiency syndrome (AIDS) or AIDS-related complex who were receiving methadone maintenance treatment. All patients were opiate users, and most were also secondary users of other substances, including stimulants and alcohol. Of 17 patients who were started on buspirone, 14 remained on medication for more than 2 weeks. Of this latter group, all showed at least temporary improvement in one or more of the following areas: subjective reduction of anxiety, reduction of prescribed benzodiazepine use, or reduction in the number of urine tests positive for drugs of abuse, particularly morphine. Buspirone was well tolerated by all but three of these patients; there was no evidence of buspirone misuse. Given its favorable adverse effects profile, buspirone may be particularly useful in the treatment of anxiety in HIV-infected drug users.