This study examines the effects of infused human atrial natriuretic peptide 1-28 (hANP) on ovine fetal renal function. hANP was infused into chronically cannulated ovine fetuses of 103-128 days gestation (term 142-152 days) at 1.1 (4), 2.2 (5), and 4.4 (5) micrograms/h for 2 h. Isotonic saline was infused in 10 control experiments. The fractional reabsorption of infused lithium was used as a marker of proximal tubular sodium reabsorption. Glomerular filtration rate and urinary water and electrolyte excretion were assessed. The blood pressure and heart rate were unaltered by any dose of hANP. The lowest dose (1.1 microgram/h) did not produce any significant changes in glomerular filtration rate, urinary electrolyte or water excretion, or fractional reabsorption of lithium. hANP, at 4.4 micrograms/h, caused a significant (p less than 0.001) 5-fold increase in the excretion of Na, Cl, and Ca, doubled the excretion rate of K and free water clearance, and significantly increased glomerular filtration rate. Fractional sodium reabsorption and fractional reabsorption of lithium were significantly decreased (p less than 0.001, less than 0.01, respectively). The results show that the fetal kidney, at this stage, is as responsive to hANP as is the adult kidney. The natriuretic action of hANP is related to increases in glomerular filtration rate and proximal tubular rejection of sodium (as assessed by fractional reabsorption of lithium). The excessive salt loss of the premature or low birth weight neonate, which also involves increased delivery of filtrate to the distal tubule, may be due to endogenous hANP, circulating at high concentrations.