m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means +/- S.D. of plasma prolactin concentrations before treatment, 12 h, and 1, 2 and 3 weeks after initiation of treatment were 9.1 +/- 5.6, 14.7 +/- 9.1, 15.3 +/- 8.5, 13.2 +/- 7.0 and 13.0 +/- 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h (p < 0.01), 1 week (p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.