The role of the atrial natriuretic factor and of the main counteracting sodium-retaining principle, the renin-aldosterone system, in acute volume regulation of cirrhosis of the liver has been investigated. Central volume stimulation was achieved in 21 patients with cirrhosis, 11 without and 10 with ascites, and 25 healthy controls by 1-hr head-out water immersion. Immersion prompted a highly significant (p less than 0.001) increase of atrial natriuretic factor plasma concentrations in cirrhotic patients without ascites from 8.5 +/- 1.3 fmoles per ml to 16.5 +/- 2.6 fmoles per ml, comparable to the stimulation in control subjects (6.0 +/- 0.6 fmoles per ml to 13.6 +/- 2.6 fmoles per ml). In cirrhotic patients with ascites, atrial natriuretic factor increase (from 7.7 +/- 1.3 fmoles per ml to 11.4 +/- 2.3 fmoles per ml) was blunted (p less than 0.05). Plasma renin activity and plasma aldosterone concentration were elevated in cirrhotic patients, especially in the presence of ascites. Following immersion, plasma renin activity and plasma aldosterone concentration were reduced similarly in all groups. Water immersion induced a more pronounced natriuresis and diuresis in control subjects than in cirrhotic patients. Neither atrial natriuretic factor nor plasma renin activity nor plasma aldosterone concentration alone correlated to sodium excretion. However, atrial natriuretic factor to plasma aldosterone concentration ratios were closely correlated to basal and stimulated natriuresis in cirrhotic patients, particularly in those with ascites. These data suggest that atrial natriuretic factor and the renin-aldosterone system influence volume regulation in patients with cirrhosis.