Very few studies have examined the role of serotonin (5-HT) in the modulation of craving for cocaine in cocaine-addicted persons. The authors evaluated whether the acute increase in serotonergic neurotransmission after the administration of a challenging dose of the 5-HT partial agonist meta-chlorophenylpiperazine (m-CPP) had an effect on spontaneous cocaine craving. Male inpatients (N = 31) who met DSM-III-R criteria for cocaine dependence completed 2 days of testing (separated by 48 hours) that involved the oral administration of m-CPP (0.5 mg/kg of body weight) or placebo in random order and under double-blind conditions. Patients' craving for cocaine was found to decrease significantly after the administration of m-CPP. These data could provide evidence for a modulation of cocaine craving by 5-HT systems.