The angiotensin II analogue 1-sar-8-ala-angiotensin II (saralasin) was infused i. v. into 6 patients with stable nephrotic syndrome on a 110–120 mEq/day sodium intake. After two 60-min control periods (C<sup>+</sup>) saralasin was infused during two 30-min periods at a rate of 2 and 5 µg/kg/min, respectively, followed by 10 µg/kg/min for an additional 60 min and a subsequent control period of 60 min. Saralasin increased arterial blood pressure in a dose-dependent fashion from a mean of 126/88 (C<sup>+</sup>) to 145/109 mm Hg (10 µg/kg/min), while glomerular filtration rate fell from a mean of 145 ± 17 (C<sup>+</sup>) to 118 ± 21 ml/min (10 µg/kg/min). Urinary Na<sup>+</sup> and K<sup>+</sup> excretion was unchanged during the 2 and 5 µg/kg/min infusion rate, but fell by a mean of 31 and 21%, respectively, during the 10 µg/kg/min infusion dose of saralasin. Control ‘recumbent’ plasma renin activity and plasma aldosterone concentration were within the normal range for the established sodium intake. Mean PRA decreased dose-dependently from 1.86 ± 0.43 (C<sup>+</sup>) to 1.27 ± 0.40 ng/ml/3 h (10 µg/kg/min). However, plasma aldosterone concentration was unaffected during the low dose of saralasin, increased during the 5 µg/ kg/min dose (C<sup>+</sup>: 43.7 ± 8.5; 5 µg/kg/min: 78.4 ± 13.7 pg/ml), and returned into the control range during the 10 µg/kg/min infusion dose. Thus, saralasin at lower doses exhibited an angiotensin II agonistic effect on all receptor systems studied. Our findings exclude a major role of the renin-angiotensin-aldosterone system in the pathophysiology of impaired sodium balance in patients with nephrotic syndrome. They do, however, further support the hypothesis of functional differences between the vascular and adrenocortical angiotensin II receptors.