Prostaglandins of the E (PGE) series have long been considered ''catabolic'' hormones, but recent data suggest that they may be secreted in critically ill patients to counteract stress hormones, stimulating protein synthesis. Their use is under scrutiny to improve hepatic microcirculation and as cytoprotective agents. We tested the effects of PGE 1 on hepatic and whole-body nitrogen metabolism in eight patients with cirrhosis. Urea-nitrogen synthesis rate, โฃ-amino-nitrogen levels, and nitrogen exchange were measured in the basal, postabsorptive state and in response to continuous alanine infusion, in paired experiments, during superinfusion of PGE 1 or saline. Splanchnic and systemic hemodynamics were assessed by echo-Doppler at the beginning and at the end of each experiment. PGE 1 produced a rapid fall in plasma amino acids and in urea-nitrogen synthesis rate, as well as a positive nitrogen exchange. The slope of the regression of โฃ-amino-nitrogen levels on urea-nitrogen synthesis rate, a measure of liver cell metabolic activity, was not affected, but the regression line was shifted rightward, suggesting a nitrogen-sparing effect of PGE 1 . Mesenteric artery and portal flow were unchanged, whereas femoral artery flow increased by 30%. Insulin and glucagon levels were not systematically different. We conclude that PGE 1 reduces hepatic urea synthesis rate, independent of hormones and/or hepatic flow, possibly acting at the peripheral level on amino acid transport, thus reducing amino acid supply to the liver. The resulting net nitrogen sparing might be the basis for the beneficial effect of PGE 1 in clinical hepatology. (HEPATOLOGY 1998;27:815-821.) Prostaglandins (PGs) are produced locally and act as interor intracellular modulators of biochemical processes in the tissues where they are formed. They have significant effects on amino acid/protein metabolism, but results are conflicting. [1][2][3][4][5][6] Because of their increase in inflammatory processes and catabolic stress, it has long been supposed that PGs might be Abbreviations: PG, prostaglandin; FHNC, functional hepatic nitrogen clearance; UNSR, urea-nitrogen synthesis rate; TBW, total body water.