We studied the prolactin and cortisol responses to the 5-HT releasing agent, D-fenfluramine in 31 drug-free depressed patients and 29 healthy controls, using a double-blind, placebo-controlled design. There was no difference in either endocrine response between depressives and controls. Examining the sexes separately, or restricting comparisons to patients with melancholic depression, did not lead to any differences between the groups. Our findings suggest that in contrast to other 5-HT neuroendocrine probes such as L-tryptophan and clomipramine, the prolactin response to fenfluramine are not consistently blunted in depressed patients.