F2-isoprostanes (F2-IP) and 4-hydroxynonenal (4-HNE), peroxidation products of polyunsaturated fatty acids (PUFA), are considered the most reliable indicators of endogenous lipid peroxidation in vivo. To determine to what extent these are also altered in patients with alcoholic liver disease, plasma free and esterified F2-IP as well as 4-HNE were measured by GC/MS in 49 fasting subjects who underwent diagnostic percutaneous needle biopsies of the liver. Compared to patients with mild steatosis and no fibrosis, free F2-IP and 4-HNE were strikingly increased in individuals with alcoholic hepatitis. There was also a significant but lesser rise of 4-HNE in patients with perivenular fibrosis. An increase of F2-IP was also found in subjects with transition to, or complete, alcoholic cirrhosis, with a comparable trend for 4-HNE. By contrast, in patients who were drinking heavily up to 48 hr before admission, F2-IP were not abnormal, but they increased later (p < 0.005). Contrasting with plasma free F2-IP, esterified F2-IP were not significantly changed with fibrosis. Thus, whereas circulating esterified F2-IP were unchanged in patients with alcoholic liver disease, there was an increase in free F2-IP as well as 4-HNE during recovery from intoxication. The increase was not a result of accompanying hepatitis C but a function of the stage of alcoholic liver injury, possibly reflecting enhanced lipid peroxidation as well as interference with biliary excretion and/or hepatic esterification.