Hepatic fine structural alterations induced by shortterm administration of the hypolipidemic drug oxandrolone were evaluated using morphometric techniques. These changes are described in the livers of normolipidemic young adult and hyperlipidemic retired breeder male rats. Retired breeder rats, characterized by hyperlipidemia and a high incidence of arteriosclerosis, are thought to undergo premature aging. A previous morphometric study has shown that the hepatocytes of retired breeder rats are larger, contain a greater volume fraction of lysosomes, and have significantly less smooth-surfaced endoplasmic reticulum than those of young adult rats. However, after oxandrolone administration, the livers of these two animal groups were no longer distinguishable on the basis of these morphometric parameters. Unlike a number of other hypolipidemic drugs, oxandrolone does not induce a marked proliferation of hepatic microbodies. The effect of oxandrolone on the livers of prematurely aging rats suggests that the age-related fine structural changes are not the result of irreversible alterations in the genome or translation-transcription apparatus but may actually represent secondary reactions to extrahepatic and/or endocrine metabolic changes. The relationship between (1) aging and hyperlipidemia and (2) aging and the reduced hepatic capacity to metabolize drugs suggest a need to evaluate the effects of lipid-lowering drugs on the livers of old as well as young animal models.