We have previously described an association between higher serotonin (5-HT) responsivity, indexed by prolactin response to D-fenfluramine challenge, and poorer treatment response to haloperidol in non-medicated schizophrenics. The aim of the present study was to investigate the effects of antidopaminergic treatment on the prolactin response in the repeated challenge test. D-Fenfluramine was administered to 22 young, acutely ill schizophrenics (11 females and 11 males) after 4 weeks of haloperidol treatment. Whereas neuroleptic administration significantly raised basal prolactin levels (P < 0.0001), subsequent D-fenfluramine challenge produced an additional significant increase (P < 0.001). Moreover, the magnitude of this increase was not different from the pretreatment response. Our results demonstrate that prolactin response to the challenge is mediated through the 5-HT system. An observed negative association between posttreatment prolactin response and therapeutic response to haloperidol did not reach statistical significance.