In non-cirrhotic patients, splanchnic, renal and pulmonary vascular beds are involved in the plasma clearance for atrial natriuretic peptide (ANP). In patients with cirrhosis, endogenous plasma ANP clearance by these vascular beds has not been systematically studied. In addition, the influence of the severity of liver failure on plasma ANP clearance is not known. Thus, in this study we determined plasma ANP clearance by splanchnic, renal and pulmonary circulations using both arteriovenous differences in plasma ANP concentrations and organ plasma flow in 11 patients with cirrhosis. The role of forearm circulation in plasma ANP extraction was also studied. Splanchnic plasma ANP extraction was 29 +/- 7% (mean +/- S.E.) and splanchnic plasma ANP clearance was 404 +/- 130 ml/min (n = 7). Renal plasma ANP extraction and clearance were 32 +/- 8% and 191 +/- 57 ml/min, respectively. Forearm plasma ANP extraction was 11 +/- 4%. Pulmonary plasma ANP extraction and clearance were 8 +/- 5% and 312 +/- 272 ml/min, respectively. A significant negative correlation was found between logarithm of serum bilirubin concentration, on one hand, and splanchnic and forearm plasma ANP extraction, on the other. A significant negative correlation was found between Pugh's score, on one hand, and renal plasma ANP extraction and clearance, on the other. No significant correlation was found between the severity of liver failure and pulmonary plasma ANP extraction and clearance. As a result, we conclude that in cirrhotic patients splanchnic, renal, forearm and pulmonary vascular beds are involved in plasma ANP extraction and clearance. Plasma ANP extraction and/or clearance may be attenuated in the splanchnic, renal and forearm circulations due to liver failure.