Hypertension is an early manifestation of autosomal dominant polycystic kidney disease (ADPKD). Whether polycystic kidneys have an intrinsic abnormality that leads to sodium retention, volume expansion, and hypertension is uncertain. We studied the natriuretic response to a 4-hour infusion of physiologic saline at a rate of 6.5 ml/kg per hour in 10 patients with ADPKD who had normal renal function and 10 gender- and age-matched control subjects. Baseline 24-hour urinary excretions of sodium and potassium were similar in both groups. The baseline filtration fraction was significantly higher in the patients with ADPKD than in the control subjects. During the infusion of saline, no significant changes in blood pressure, clearance of inulin, or clearance of p-aminohippuric acid were detected. The increase in fractional excretion of sodium over baseline was significantly higher in the patients with ADPKD than in the control subjects. The pressure-natriuresis regression line was significantly shifted to the right in patients with ADPKD who had hypertension. The fractional excretion of potassium was significantly lower in patients with ADPKD than in control subjects. No significant differences in plasma renin activity, aldosterone, or atrial natriuretic factor were detected between the two groups. These observations suggest the presence of subtle abnormalities in the management of renal sodium that might contribute to the development and maintenance of hypertension in patients with ADPKD.