The effect of oxytocin on the ACTH, cortisol, GH and PRL response to physical exercise was investigated in 6 normal men. In addition, the possible involvement of endogenous opioids in the mediation of oxytocin action was evaluated. After fasting overnight, each subject was tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 20 min in all subjects. Tests were carried out under administration of oxytocin (2000 mIU as an iv bolus injection plus 32 mIU/min per 30 min) or naloxone (10 mg as an iv bolus injection) alone; furthermore, the effect of oxytocin together with naloxone (10 mg as an iv bolus injection) was evaluated. In the remaining test, normal saline was given instead of drugs. Plasma ACTH, cortisol, PRL and GH concentrations were significantly increased by physical exercise. Administration of oxytocin, naloxone or their combination was without effect on the PRL and GH rise elicited by exercise. In contrast, the exercise-induced ACTH and cortisol response was significantly raised by naloxone and reduced by oxytocin. When oxytocin was preceded by administration of naloxone, the ACTH and cortisol response to exercise was not reduced by oxytocin. These data show that oxytocin is capable of inhibiting the rise in ACTH and cortisol, but not in GH and PRL induced by physical exercise. Since naloxone abolished the inhibitory effect of oxytocin, oxytocin action on ACTH and cortisol secretion might be supposed to be mediated by an opioid pathway.(ABSTRACT TRUNCATED AT 250 WORDS)