Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and “over-the-counter” drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug-Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men. Characterization of concomitant medication use in clinical trials may allow the design of studies that better reflect current clinical treatment standards and patient preferences, contribute to a more accurate evaluation of drugs being investigated, and provide preliminary indication of effects, toxicities, and costs of commonly used medications specifically in HIV-infected patients. As the number of agents demonstrated to be efficacious in the treatment of HIV infection and the potential for significant drug interaction increase, the assessment of concomitant medication use by HIV-infected patients will be vitally important.