Experiments were performed to study the effects of opioids on both the plasma arginine vasopressin and renal responses to hypertonic saline. Neither the opiate antagonist naloxone nor the enkephalin agonist DAMME [D-Ala2, MePhe4, Met (0)-ol)enkephalin] altered the vasopressin response to the same hypertonic stimulus, although DAMME increased free water clearance. In man, opioids do not seem to be important mediators of the vasopressin response to osmolar change.