It is shown that peroxidation of phosphatidylcholine (PC) is enhanced in liver of mice fed a hepatocarcinogenic choline-deficient diet containing 0.1% w/w ethionine. Mice were divided into 4 groups and fed for 4 weeks one of the following diets: choline-supplemented; choline-supplemented containing ethionine; choline-deficient; and choline-deficient containing ethionine. Phosphatidylcholine hydroperoxide (PCOOH) of liver lipids was measured by high performance liquid chromatography using a chemiluminescence detector. Mice fed a choline-deficient diet containing ethionine showed 6-fold higher PCOOH levels than the choline-supplemented control mice: the PCOOH/PC molar ratios of liver lipids were 32.3 X 10(-5) and 5.6 X 10(-5), respectively. In addition to this remarkable degree of lipid peroxidation in liver of mice fed the choline-deficient diet containing ethionine, we also observed a significant liver fatty infiltration, a decrease in plasma and liver alpha-tocopherol, and an increase in liver injury-indicative enzyme activities. Also, marker enzymes for hepatocarcinogenesis, glucose-6-phosphatase and gamma-glutamyl transpeptidase were affected. These data suggest that enhanced hydroperoxidation of phosphatidylcholine may participate in hepatocarcinogenesis provoked by choline deficiency in the presence of ethionine.