The efficacy and safety of alprazolam and buspirone for treating generalized anxiety disorder (GAD) were compared in a 6-week, double-blind, randomized, placebo-controlled study of 94 outpatients. Mean daily doses at the end of the study were 1.9 mg alprazolam and 18.7 mg buspirone. As judged by the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Physician's Global Improvement Scale, and other efficacy scales, alprazolam and buspirone were similar in efficacy, but more effective than placebo, for treating anxiety and depression symptoms in these patients. Clinically important differences were noted between drugs in the onset of effect, with alprazolam producing rapid and sustained improvement within the first week of treatment and buspirone producing more gradual, continuous improvement throughout the study. Significantly more buspirone-treated than alprazolam-treated patients failed to complete the study, primarily because of side effects or inefficacy. No clinically important differences were noted between alprazolam and buspirone in side effects, vital signs, or laboratory test results. Alprazolam-treated patients most frequently reported central nervous system-related side effects (drowsiness and sedation), while buspirone-treated patients most frequently reported gastrointestinal system-related side effects (appetite disturbances and abdominal complaints).