ABSTRACT It has been suggested that serotonin (5HT) function is abnormal in alcoholics even during abstinence. The prolactin response to fenfluramine (PRF) is generally believed to reflect the activity of the 5HT system and has been previously used to investigate 5HT activity in a variety of conditions, including alcoholism. The origin of the cortisol (CORT) response to fenfluramine is less clear. The objectives of this paper are to examine the prolactin (PRL) and CORT response todl-fenfluramine in a large cohort of males with alcohol dependence who had been abstinent for 3 weeks, and to compare this with an age-matched control group. Ninety-four subjects with a DSM-III-R diagnosis of moderate to severe alcohol dependence who had been abstinent for 3 weeks, and 23 control subjects underwent neuroendocrine challenge withdl-fenfluramine (10 mg per 10 kg body weight). PRL and CORT responses were measured. No significant difference was found in PRF between abstinent, alcoholic patients and controls (F = 2.7, d.f. = 1.115, P = 0.10). CORT response was significantly lower in abstinent alcoholics than in controls (F = 10.0, d.f. = 1.116, P = 0.002). The results suggest no clear difference in 5HT function between abstinent alcoholics and healthy controls. The reduced CORT response in abstinent alcoholics further supports evidence of hypofunction of the adrenocortical system in this group.