To evaluate the influence of changes in liver function on serum levels of melatonin, we measured serum levels and MCR of the hormone in patients with liver cirrhosis and in healthy control subjects. Daytime (0900–1100 h) serum levels of melatonin in patients with liver cirrhosis were significantly elevated compared to those i n healthy subjects. Significant positive correlations of the daytime serum levels of melatonin with the serum retention rate of indocyanine green dye and serum levels of total bilirubin were noted. The clearance of melatonin from blood showed a biphasic first-order kinetic pattern. The half-life of each phase was significantly prolonged in patients with cirrhosis compared to healthy subjects. Our data indicate that the elevated daytime serum levels of melatonin in patients with liver cirrhosis are due to decreased clearance, probably related to decreased liver bloodflow,lowered activity of 6β-hydroxylase, and competition with bilirubin in the intrahepatic transport system. (J Clin Endocrinol Metab54: 1025, 1982)