Prolactin and cortisol responses to fenfluramine (60 mg PO) challenge were examined in 20 subjects (10 manic patients and 10 age- and gender-matched healthy controls) to ascertain the "net" central serotonin (5-HT) activity in mania. There was no difference in baseline prolactin or cortisol levels between manic patients and healthy controls. Similarly, neither prolactin nor cortisol response to fenfluramine was different in manic patients compared to controls. There was also no correlation between severity of symptoms in manic patients and prolactin or cortisol response to fenfluramine challenge. The results do not support the possibility that net central 5-HT activity is altered in mania.