Nine adult patients with the nephrotic syndrome were studied during 4 hours of water immersion (WI) to the level of the neck in the seated position and under control conditions. During WI, sodium excretion (UNaV) rose from a mean prestudy level of 45.9 +/- 18.7 microEq/min to a mean peak level of 242.2 +/- 42.8 microEq/min during the 4th hour. During control studies, UNaV was unchanged. During WI, urine volume rose from 1.1 +/- 0.4 ml/min and reached a peak level of 7.5 +/- 0.8 ml/min during the 2nd hour. There were also marked increases in free water clearance and potassium excretion. Plasma renin activity fell from a prestudy level of 5.1 +/- 1.3 ng/ml/hr to a nadir of 1.9 +/- 0.4 ng/ml/hr during the 2nd hour of WI. Levels were unchanged during control studies. There was a considerable variation in the magnitude of the natriuretic effect of WI between the individual patients. Peak levels of UNaV varied from 55.3 to 488 microEq/min, and net negative sodium balance varied from 12.8 to 105 mEq. These variations were found to be directly related to the patient's estimated plasma volume, such that y = 19.2 chi - 211 (r = 0.84) represented the relationship between the plasma volume and the peak UNaV, and y = 1.9 chi - 41 (r = 0.81) represented the relationship between plasma volume and net negative sodium balance. These studies indicate that in patients with nephrotic syndrome, as in normal subjects, WI provides a potent natriuretic stimulus that results from expansion of the central blood volume. The magnitude of the natriuresis in nephrotic patients is related to their plasma volume, an observation that might help predict therapeutic benefit of the procedure in the individual patient.