The responsiveness of atrial natriuretic factor (ANF) to central volume expansion and its role as a determinant of the natriuretic and diuretic responses of cirrhotic patients was evaluated utilizing water immersion (WI). Following equilibration on a 10-mEq sodium diet, 9 seated cirrhotic patients were studied during 3 h of WI. Before WI, plasma ANF levels (10.9 ± 2.4 fmol/ml) were similar to those previously observed in normal sodium-replete subjects (7.7 ± 0.9 fmol/ml). Five of the 9 cirrhotic subjects manifested an exaggerated peak ANF response, whereas the remaining 4 manifested increases similar to those of normals. The concomitant natriuretic response varied widely, ranging from absent to markedly exaggerated responses. The peak urinary sodium excretion varied independently of peak plasma levels of ANF and peak change of ANF from the prestudy hour (r = 0.36, p > 0.20, and r = 0.46, p > 0.20, respectively). Thus, in contrast to normal subjects, in whom the immersion-induced natriuresis correlated closely with the changes in ANF, the natriuretic responses of cirrhotic patients were dissociated from the concomitant increases in ANF. These observations indicate that sodium retention in cirrhosis is not attributable to impaired ANF releas