Ten healthy male subjects were administered i.v. meta-chlorophenyl-piperazine (MCPP) (0.1 mg/kg) after oral ritanserin (5-10 mg), a putative 5HT1c/5HT2 (serotonin) antagonist, or placebo. Behavioral responses, cardiovascular effects, and neuroendocrine responses (cortisol, growth hormone, and prolactin) were measured serially for 4 hours after MCPP infusion. Premedication with ritanserin attenuated the MCPP-induced increases in self-rated anxiety and prolactin, and completely antagonized MCPP cortisol elevations. In contrast, ritanserin did not significantly alter growth hormone response to MCPP. These findings suggest a role for 5-HT1c/5-HT2 receptors in the endocrine and behavioral responses to the mixed serotonin agonist MCPP in humans.