The etiology and optimum treatment of panic disorder remain unclear. Imipramine and alprazolam are reasonably well established treatments. Several reports have suggested that serotonin reuptake inhibitors may also be effective for this condition. To investigate this issue, 27 published or presented placebo-controlled, double-blind studies of DSM-III or DSM-III-R panic disorder were subjected to meta-analysis. The serotonin reuptake inhibitors included paroxetine, fluvoxamine, zimelidine, and clomipramine. The standard treatments were imipramine or alprazolam. All three treatments were highly significantly superior to placebo in alleviating panic. The serotonin reuptake inhibitors were also significantly superior to both imipramine and alprazolam. The superiority of the serotonin reuptake inhibitors remained, but was less pronounced, when they were compared to the studies which used higher doses of imipramine or alprazolam. These findings underscore the importance of serotonin reuptake inhibitors in the treatment of panic disorder and indirectly add to the evidence that serotonergic abnormalities may have a role in its etiology.