Effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) on renal function were studied in anesthetized dogs and isolated perfused rat kidneys. Two doses of alpha-hANP were used to determine whether renal hemodynamics or tubular reabsorption is tha major factor in the diuretic action of alpha hANP. The excretion rates of sodium (Na) and inorganic phosphate (PO4) were evaluated to determine the site of diuretic action in the renal tubule. In dogs that received the smaller dose of alpha-hANP (5 ng.kg-1.min-1) infused into the renal arteries without changes in systemic or renal hemodynamics, urine volume (UV) and urinary Na excretion (UNaV) increased significantly. Fractional excretion of Na (FENa) was increased, while fractional excretion of PO4 (FEpo4) was unchanged, following the infusion of alpha-hANP. The calculated fractional Na reabsorption in the distal tubule (DTRNa) during the infusion of alpha-hANP was significantly suppressed. In dogs that received the a larger dose of alpha-hANP (50 ng.kg-1.min-1), the glomerular filtration rate (GFR), UV, and FENa were increased and DTRNa was decreased. In isolated rat kidneys perfused at a constant pressure, a lower concentration of alpha-hANP (0.5 ng.ml-1) in the perfusate caused diuresis and increased Na and PO4 excretion without any renal hemodynamic alterations. A higher concentration of alpha-hANP (5 ng.ml-1) increased GFR, Na and PO4 excretion. Since PO4 reabsorption is believed to occur primarily in the renal proximal tubule, these findings suggest that the diuretic action of alpha-hANP in smaller doses in induced by direct action on renal distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)