Intravenous infusion of graded doses of alpha-human atrial natriuretic polypeptide (alpha-hANP) resulted in a dose-dependent decrease in blood pressure and an increase in heart rate in 11 healthy male volunteers. However, there were no significant changes in urine output or in the urinary excretion rate of sodium. Glomerular filtration rate did not change, while renal blood flow decreased, leading to significant increases in filtration fraction and renal vascular resistance. Although plasma renin activity (PRA) and plasma concentration of norepinephrine (PNE) increased during infusion of alpha-hANP (both p less than 0.001), plasma concentrations of aldosterone (PA) and cortisol (PC) decreased (both p less than 0.001). Plasma concentration of arginine vasopressin (PAVP) did not change during the infusion, but greatly increased after cessation of the infusion. The hematocrit increased slightly, but significantly, during the infusion. These results show that, although alpha-hANP has a potent hypotensive action and inhibits the secretion of aldosterone, cortisol, and probably arginine vasopressin, it does not dilate renal vessels in normotensive persons, and likely increases vascular permeability. The lack of consistent diuretic and natriuretic responses to alpha-hANP may be related to the predominance of the hypotensive effect over the renal effects of the peptide in normotensive persons, or a diurnal change may have served to obscure such a response.