Carbon tetrachloride (CCl4) is metabolized to trichloromethyl radical and induces liver injury with elevated serum transaminase and increased hepatic triacylglycerols (TG). To answer the question whether dietary polyunsaturated fatty acids (PUFA) enhance free radical-mediated liver injury, a docosahexaenoic acid (DHA)-rich fish oil (FO) or a saturated and monounsaturated fatty acid-rich beef tallow diet was fed to mice for 4 wk and then CCl4 was administered. When thiobarbituric acid-reactive substances (TBARS) were measured in the absence of antioxidant, the FO diet and CCl4 treatment markedly increased liver TBARS values synergistically, apparently supporting the interpretation that the highly autoxidizable DHA accelerates lipid peroxidation induced by CCl4,. However, no such marked interaction was observed between diet and CCl4 treatment in liver TBARS values measured in the presence of an antioxidant in the assay mixtures as well as in conjugated diene contents. Furthermore, the FO diet did not enhance CCl4- induced elevation of serum transaminase but lowered liver TG levels. The proportion of DHA, the most easily autoxidizable among common PUFA, was increased but those of eicosanoid precursors were decreased in liver phospholipids by CCl4 treatment, possibly reflecting the inflammation-related mobilization of eicosanoid precursors but not lipid peroxidation. these results indicate that dietary enrichment with DHA does not enhance CCl4-induced liver injury through the so-called free radical-mediated propagative autoxidation of DHA in mice.