Two different doses of d-fenfluramine HCl and d,l-fenfluramine HCl (0.5 mg/kg and 1.0 mg/kg) were administered to 11 healthy male volunteers to compare the neuroendocrine responses to these two forms of fenfluramine in human subjects. Prolactin (PRL) responses to d- and d,l-fenfluramine were significantly greater than those to placebo and were equivalent at both dose levels. Adrenocortiatrophic-releasing hormone (ACTH) and cortisol (CORT) responses to d-fenfluramine at both dose levels were also significantly greater than those to placebo. In contrast, the higher dose of d,l-fenfluramine was associated only with a significant CORT response in comparison to placebo. PRL responses to d-fenfluramine were higher than the PRL response to d,l-fenfluramine at either dose level. The PRL response to d-fenfluramine at 0.5 mg/kg was very highly correlated with the PRL responses to d,l-fenfluramine at 1.0 mg/kg (r = 0.97, n = 10). Homovanillic acid (HVA) were not altered by either d, or d,l-fenfluramine at either dose in a subsample of subjects (n = 4). ACTH/CORT responses to d- and d,l-fenfluramine were modestly intercorrelated. These data suggest that the PRL response evoked by d-fenfluramine is quantitatively very similar to that evoked by d,l-fenfluramine.