An oral d-fenfluramine neuroendocrine challenge test was carried out in 17 women with premenstrual depression and 14 controls, twice in each subject, once in the late luteal phase when mood change was likely to be at its worst (i.e. premenstrual) and once postmenstrually. Women weighing < 65 kg received 15 mg, the remainder 30 mg of d-fenfluramine. Although there was considerable individual variability, a substantial average prolactin response was observed in both groups but no phase, group or group X phase interaction effects were found. Oestradiol levels were significantly higher during the postmenstrual test but showed no relationship to prolactin response. Cortisol showed a more modest response to the drug and a phase effect was found, with cortisol increase being greater during the postmenstrual test in both groups. In contrast to earlier findings with i.v. L-tryptophan challenge, the present study failed to show any difference in neuroendocrine response between women with premenstrual depression and controls. These results suggest that 5-hydroxy-tryptophan, receptor function is unaltered in perimenstrual mood disorder although other interpretations of the negative findings are discussed.