Atrial natriuretic peptide (ANP), angiotensin II (Ang II), and aldosterone (Aldo) in plasma and creatinine clearance (Ccr) were determined during basal conditions in 17 patients with the nephrotic syndrome and 20 control subjects. In addition, six of the patients were studied after seven remissions of the syndrome. In the nephrotic syndrome ANP was higher than in the control group (9.7 (median) versus 7.2 pmol/l, p less than 0.01), Ccr was lower (55 versus 99 ml/min, p less than 0.01). Angiotensin II and Aldo were the same in patients and control subjects. After remission of the syndrome ANP was reduced (11.2 to 5.4 pmol/l, n = 7, p less than 0.02) and Ccr increased (52 to 84 ml/min, n = 7, p less than 0.02), whereas Ang II and Aldo were unchanged. A significant, negative correlation was found between ANP and Ccr in the subgroup of patients in whom the syndrome remitted (Q = -0.547, n = 14, p less than 0.05). Atrial natriuretic peptide was not correlated to either Ang II or Aldo in either of the groups. It is concluded that patients with the nephrotic syndrome have elevated ANP, and it is suggested that a high ANP may be a compensatory phenomenon induced by a decreased renal ability to eliminate sodium and water.