Normal controls (NC) (n = 15), patients with panic disorder (PD) (n = 13) and patients with major depression (MD) (n = 17) were challenged with a single, oral dose (0.25 mg/kg) of the selective 5HT agonist m-chlorophenyl-piperazine (MCPP) or placebo. Blood samples were assayed for cortisol and MCPP levels every 30 min. The PD group had an augmented cortisol release when compared to the other two groups. Finally, a significant correlation was found across all subjects between clinical anxiety level and cortisol release on MCPP. These data support the hypothesis of 5HT receptor hypersensitivity in PD.