The distributions of lipids of hepatic specimens obtained at autopsy from 7 adult patients who had been taking large amounts of aspirin for arthritis were compared to 7 control samples obtained from livers of autopsied adults without prior liver disease. The total neutral lipid levels of control livers were approximately one-third lower than those observed for livers of patients on aspirin. In addition, the phospholipid content of control specimens was significantly greater than that of livers from adult patients that had been on a high dose of aspirin for a long time. Examination of individual lipid classes showed that the concentrations of free fatty acids, triacylglycerols, and mono- and diacylglycerols were highest in livers of patients with aspirin exposure, and that all phospholipids were diminished. Phosphatidylcholines and phosphatidylethanolamines showed the greatest decrease. These results suggest that the livers of patients taking large amounts of aspirin may accumulate fatty acids and neutral lipids due to an impairment in the oxidation of fatty acids by hepatocytes. The data obtained also suggest that needle biopsy of the liver with measurement of distribution of hepatic lipids, perhaps together with histopathologic examination, may provide useful diagnostic information.