Plasma levels of pipecolic acid, which is a minor metabolite of lysine, were determined by high-performance liquid chromatography in 22 patients with chronic liver disease, composed of 6 patients with chronic active hepatitis, 11 with liver cirrhosis and 5 with hepatocellular carcinoma. The plasma levels of pipecolic acid, when compared to those in normal subjects (1.00 +/- 0.08 nmoles per ml), were found to be significantly elevated (p less than 0.01) in patients with liver cirrhosis (1.93 +/- 0.24 nmoles per ml) and hepatocellular carcinoma (2.22 +/- 0.49 nmoles per ml), but did not show any significant change in patients with chronic active hepatitis. Plasma levels of pipecolic acid correlated positively with serum bile acid and bilirubin, and negatively with indocyanine green disappearance rate, cholinesterase and prothrombin time but not with plasma lysine levels. These results suggest that plasma levels of pipecolic acid increase almost parallel to the severity of liver damage, and that this increase in pipecolic acid may reflect the injury of liver peroxisomes which appear to be related to the degradation of pipecolic acid.