ABSTRACT— The renal and hormonal effects of repeated atrial natriuretic peptide (ANP) boli (1 μg/kg of body weight) were studied in eight cirrhotic patients with refractory ascites. Under basal conditions the patients showed a striking activation of the renin-angiotensin-aldosterone system (plasma renin activity 19.3 ± 3.0 μg/ml±h, plasma aldosterone concentration 3.87 ± 0.58 ng/ml) and a tenfold elevation in plasma ANP levels compared to healthy subjects (131.7, range 47.0–288.6, vs. 9.8, range 5.0–15.0, fmol/ml, p < 0.001). The first ANP injection was followed by a remarkable increase in plasma ANP levels and by a slight increase in urinary cyclic guanosine-monophosphate excretion (from 1050.8 ± 454.8 to 1446.6 ± 822.2 pmol/min). A significant reduction of mean blood pressure (MBP) occurred 5 min after the first injection (from 86.7 ± 7.2 to 79.9 ± 5.8 mmHg, p < 0.05), but values gradually returned to the baseline after 30 min. Heart rate (HR) increased 10 min after the first bolus injection (from 83.75 ± 4.7 to 88.1 ± 4.6 beats/min) and reached baseline values after 30 min. Similar behaviour of MBP and HR was observed after the second, third and fourth bolus injections. Urinary sodium excretion, urinary flow, glomerular filtration rate, plasma renin activity, and plasma aldosterone concentration did not show any significant modification during ANP administration, nor did these parameters change in the following 12-h recovery period. The striking activation of the renin-angiotensin-aldosterone system and probably of other vasoconstricting and sodium-retaining systems observed in basal conditions in patients with cirrhosis and refractory ascites seems the most likely explanation for the lack of any appreciable natriuretic and diuretic effect after repeated ANP boli.