This 8-week double-blind placebo-controlled trial investigated the relative efficacy and safety of alprazolam and buspirone in the treatment of panic disorder. Alprazolam (mean +/- SD dose 5.2 +/- 2.6 mg) produced a rapid and sustained improvement in panic attacks, anxiety, phobias, and disability and was superior to buspirone (mean +/- SD dose 61 +/- 26.5 mg) and placebo on all of these measures on completer (n = 85) and endpoint analysis (n = 92). Although higher doses of buspirone were used in this study than in previous trials, buspirone was not superior to placebo on any of the outcome measures. The results were disappointing in light of buspirone's benign side effect profile and low abuse potential.