The cysteinyl leukotrienes, comprising leukotriene C4 and its metabolites, are biologically most active mediators, eliminated from the blood circulation by the liver and the kidneys. The urine of normal subjects and of patients with hepatic and/or renal failure was analysed for endogenous cysteinyl leukotrienes. The leukotriene metabolites were separated by reversed-phase high-performance liquid chromatography and subsequently quantified by radioimmunoassay. Leukotriene E4 was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol l-1 in healthy subjects to 0.8 nmol l-1 in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4 averaged 7.8 nmol l-1; in addition, N-acetyl-leukotriene E4 was detected in an average amount of 1.5 nmol l-1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 mumol leukotriene E4 mol-1 creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with severe liver disease.