In healthy men (n = 7) the renal fractional extraction of human atrial natriuretic factor (hANP) as determined by the renal venous catheter technique was approximately 50% both under basal conditions and during the administration of exogenous hANP. When arterial and venous plasma concentrations of hANP were maintained about tenfold above basal concentrations by a bolus- (100 micrograms) primed intravenous (IV) infusion (100 micrograms/h for 1 hour) of hANP, renal uptake of hANP increased from, basal, 11.2 +/- 6.7 pmol/min to 126.5 +/- 64.8 pmol/min (P less than .05), while estimated renal plasma flow (ERPF) decreased by about 25% (P less than .05). Total metabolic clearance rates (MCRs) of hANP, renal clearance rates, and production rates of hANP were 3.89 +/- 1.21 L/min, 0.42 +/- 0.18 L/min, and 76.1 +/- 52.7 pmol/min, respectively. In healthy men, one kidney accounts for about 10% of total hANP clearance.