Sodium and fluid intake were precisely regulated by 3 days of infusion of 0.07, 0.35, or 3.5 mu eq Na/min at rates of 25, 50, or 100 microliters/min in nine groups of conscious spontaneously hypertensive rats (SHR). At each level of sodium and volume intake, the acute depressor and renal responses to three doses of exogenous atrial natriuretic peptide (ANP)-(99-126) were determined in conscious, unrestrained SHR. The natriuretic responses to the highest dose of ANP-(99-126) (150 pmol/min) were independent of the rate of fluid infusion but were highly dependent on the sodium intake. The maximal increases in sodium excretion averaged 0.9 +/- 0.5 (253%), 2.6 +/- 0.5 (302%), and 15.4 +/- 2.1 mu eq.kg-1.min-1 (577%) in SHR maintained on 0.07, 0.35, and 3.5 mu eq Na/min, respectively. In addition, the diuretic but not the depressor responses to ANP-(99-126) were dependent on the sodium intake and were unrelated to the rate of fluid delivery. In separate groups of SHR, 3 days of infusions of 3.5 mu eq Na/min at 25 and 100 microliters/min significantly elevated plasma ANP from 89 +/- 16 to 200 +/- 60 and 159 +/- 24 fmol/ml, respectively. In conclusion, high sodium intake enhanced the renal responses to exogenous ANP-(99-126) despite increases in endogenous peptide concentrations in conscious SHR.