d-Fenfluramine, a specific 5-HT releasing agent without the catecholamine effects of d,l-fenfluramine, was used as a neuroendocrine challenge in 19 subjects with major depression and 19 healthy controls. Patients and controls were matched for age, sex, weight, and menstrual status. 5-HT-mediated prolactin and cortisol responses were both significantly attenuated in the depressed group. Patients with a history of a suicide attempt had lower cortisol responses than those without. Peak cortisol responses were inversely related to baseline cortisol levels. There were also significant relationships between hormone responses and both age and weight. These findings replicate those of a previous study using this challenge and reiterate the role of reduced 5-HT activity in suicide. They also reinforce the need for careful matching in neuroendocrine studies.