To assess the role of serotonin function in the development of panic anxiety, the behavioral and biochemical responses to the serotonin receptor agonist, m-chlorophenylpiperazine (MCPP) was examined in healthy subjects and agoraphobic and panic disorder patients. MCPP had anxiogenic effects in both the healthy subjects and patients. Panic attacks meeting DSM-III criteria occurred following MCPP in 12 of 23 patients and 6 of 19 healthy subjects (NS) and other ratings of anxiety also did not distinguish the two groups. MCPP resulted in significant but similar increases in cortisol, prolactin, and growth hormone in the healthy subjects and patients. The results of this investigation suggest that serotonin neuronal dysfunction may not be of etiologic significance in most panic disorder patients. However, the observed anxiogenic properties of MCPP suggest that additional studies of the role of serotonin systems in the pathophysiology of human anxiety disorders are indicated.