Changes in urinary PGE2 and PGF2 alpha excretion in chronic liver diseases were observed in relation to renal hemodynamics and sodium balance. After equilibration on a 110-170-meq sodium diet, daily urine collections were analyzed for PGE2 and PGF2 alpha by a new extraction and radioimmunoassay method. PGE2 was significantly greater in cirrhotics than in healthy subjects and in chronic hepatitis. The value was greater in cirrhotics with ascites than in those without ascites (p less than 0.05). PGF2 alpha did not differ among the groups. In cirrhotics PGE2 was correlated negatively with creatinine clearance (Ccr)(r = -0.76, p less than 0.001). After administration of 200 mg indomethacin, a significant fall in Ccr was seen only in cirrhotics with ascites. The percentage fall in PGE2 after indomethacin correlated with that in Ccr (r = 0.89, p less than 0.05) and with that in urinary sodium excretion (r = 0.68, p less than 0.02). These results suggest that PGE2 is essential in the maintenance of renal function in liver cirrhosis with ascites.