In order to investigate the relationship between the hypotensive and natriuretic effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) and sodium state, alpha-hANP was chronically administered for 7 days using an osmotic minipump (100 ng/h) to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) which had been fed either a low- (13.8 mumol/g) or high- (1380 mumol/g) sodium diet. Systolic blood pressure (SBP) and urinary sodium excretion (UNaV) were measured before and during infusion. The SBP in both SHR and WKY fell significantly within 1 day of infusion, and remained reduced for all 7 days, regardless of the sodium intake. The UNaV increased significantly in sodium-replete SHR and WKY compared with rats infused with vehicle, but remained unchanged in sodium-deplete rats. Extracellular fluid volume may be an important determining factor in the natriuretic action of alpha-hANP, but may not affect its hypotensive action.