Increased as well as decreased plasma concentrations of the endothelins, endogenous vasoactive peptides, have been reported in cirrhosis. This might be caused by alterations of hepatic or renal clearance or release. Therefore, the aim of the current study was to investigate the influence of splanchnic and renal passage and of liver function on plasma concentrations of endothelin-1 (ET-1) and endothelin-3 (ET-3) in patients with cirrhosis compared with controls. Eighteen patients with cirrhosis and 8 normotensive controls of similar age were investigated. Arterial and venous plasma samples were obtained simultaneously, and ET-1 and ET-3 concentrations were determined in extracted plasma by two separate radioimmunoassays. Arterial as well as hepatic and renal venous concentrations of ET-1 in cirrhosis (17.8 +/- 0.8 pg/mL, 19.1 +/- 0.9 pg/mL, and 16.8 +/- 0.8 pg/mL) were significantly (P < .001) higher than in controls (9.2 +/- 1.7 pg/mL, 9.0 +/- 2.0 pg/mL, and 8.4 +/- 1.9 pg/mL, respectively). The same held true for the corresponding ET-3 plasma concentrations in cirrhosis (19.3 +/- 1.6 pg/mL, 20.5 +/- 1.5 pg/mL, and 18.4 +/- 1.5 pg/mL, respectively) compared with controls (11.1 +/- 1.8 pg/mL, 11.3 +/- 1.5 pg/mL, and 10.1 +/- 1.7 pg/mL, respectively; P < .01). There was a significant (P < .05) renal net extraction of ET-1 and ET-3 in cirrhosis. In contrast, a significant (P < .05) net release of ET-1 and ET-3 (2.40 +/- 0.80 ng/min and 1.75 +/- 1.16 ng/min) during splanchnic passage was observed in cirrhosis, but not in controls (-0.24 +/- 0.51 ng/min, and -0.46 +/- 0.64 ng/min).(ABSTRACT TRUNCATED AT 250 WORDS)