To verify if exogenous prostaglandin E₂ (PGE₂) is able to release antidiuretic hormone (ADH) and if endogenous angiotensin II plays a role in this eventual PGE₂-induced stimulation of vasopressin, increasing doses of PGE₂ were infused in 6 normal volunteers before (PGE₂ study) and after the administration of 100 mg of captopril (captopril study). PGE₂, even at an infusion rate of 40 and 60 ng/kg/min, did not modify blood pressure when it was infused alone; a significant fall of blood pressure was observed, in contrast, in the captopril study. PGE₂ alone doubled the plasma levels of ADH. One hour after the subjects had been pre-treated with captopril, plasma levels of ADH fell by about 38%, then they increased by about 60% during the infusion of PGE₂. These results suggest that in normal man endogenous angiotensin II is an important non-osmotic regulator of plasma ADH and that exogenous PGE₂ can stimulate maximally the release of ADH only when the renin-angiotensin system is not impaired.