Eighteen patients with essential hypertension were separated into 2 groups, renin-unresponsive and renin-responsive, on the basis of their plasma renin response when challenged by furosemide and upright posture. The response to acute infusion of hypertonic saline solution (1.4% saline solution at a rate of 0.3 ml/min/kg over 60 minutes) was then studied. In the renin-unresponsive group, peak rate of fractional excretion of sodium and peak urine flow after saline loading were 7.6 +/- 0.7% and 476 +/- 34 ml/hour, respectively, and peak value of atrial natriuretic polypeptides (ANP) was 784 +/- 140 pg/ml. In the renin-responsive group, the values were 3.1 +/- 0.4%, 194 +/- 29 ml/hour and 115 +/- 33 pg/ml. Both fractional excretion of sodium, urine flow and ANP response were significantly higher (p less than 0.01) in the renin-unresponsive group. Moreover, a highly significant relation (r = 0.82, p less than 0.01) was observed between fractional excretion of sodium and ANP levels in all hypertensive patients. The degree of saline-induced natriuresis was not related to blood pressure, heart rate, endogenous creatinine clearance, antidiuretic hormone or preexisting level of aldosterone. Plasma renin activity changed little in either group during saline infusion, but tended to be higher at all times in the renin-responsive patients. The present findings suggest that the enhanced secretion of ANP is an important determinant for exaggerated natriuresis observed in patients with renin-unresponsive hypertension.