Volume-loading and intravenous infusion studies have suggested that the natriuretic response of atrial natriuretic factor (ANF) is blunted or unaltered during pregnancy, but these findings may be influenced by changes in peripheral metabolism or clearance. To better define the direct renal actions of ANF, three doses (0.3, 1.5, and 3.0 pmol.kg-1.min-1) of ANF were infused directly into the renal artery of nonpregnant (n = 7) and 115- to 135-day pregnant (n = 6) unilaterally nephrectomized conscious sheep. Each dose was administered on a separate day according to a protocol that consisted of two 20-min control periods, two 20-min ANF infusions, and three 30-min recovery periods. The levels of basal mean arterial pressure averaged 86 +/- 25 mmHg and were similar and constant throughout all protocols in nonpregnant and pregnant ewes. Glomerular filtration rate (GFR) and renal blood flow (RBF) were increased during pregnancy, but GFR, RBF, and fractional proximal tubular reabsorption were not significantly altered by infusion of ANF. Nonpregnant sheep exhibited a selective renal response that was limited to an increase in urinary sodium excretion (UNaV). Pregnant sheep exhibited a selective renal response that included increases in UNaV and urine flow rate produced by suppression of distal sodium and, presumably, fluid reabsorption. The natriuretic and diuretic response of pregnant sheep was much greater than that of nonpregnant sheep despite a smaller proportional increment in intrarenal ANF concentration. These data suggest that the ovine renal response to ANF is limited to actions on the distal tubule that are enhanced during pregnancy.