meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.