The role of opioids in endocrine regulation has been the subject of numerous studies. Surprisingly, however, the acute endocrine effects of morphine on basal hormonal levels in man have not been adequately documented. We report here the effects of intravenous morphine (5 mg) on plasma cortisol and prolactin. Fourteen healthy volunteers (nine male, five female) received morphine at 0930 hr. Blood samples were collected immediately before and 30, 60, 90, 120 and 180 min after the injection. In six of the male subjects the procedure was repeated with a placebo (normal saline) injection. Morphine stimulated prolactin release. There was a trend for a greater response in females compared to male subjects. Cortisol secretion was markedly suppressed by morphine. In sharp contrast to the results obtained with placebo, cortisol levels following morphine declined progressively at a rate consistent with the half-life of cortisol. This downward trend of cortisol values continued uninterrupted for the duration of the experiment in all 14 subjects. These results are consistent with the presence of an inhibitory opioid mechanism in the human hypothalamo-pituitary-adrenal axis.