The retired breeder rat, an animal known to undergo premature aging and to develop hypercholesterolemia, was studied to determine the effect of oxandrolone, a synthetic hypolipidemic steroid, on serum lipoprotein subfractions. The methods utilized for this study included density ultracentrifugation, electron microscopic lipoprotein particle sizing, and disc gel electrophoresis. The data confirmed the cholesterol-lowering ability of oxandrolone and demonstrated that its effect on total serum cholesterol was limited to the low and high density lipoprotein subclasses. The drug-treated group had 50% less LDL cholesterol and 25% less HDL cholesterol. Though there was an absolute decrease in total serum cholesterol in both these fractions, there was a re-distribution of cholesterol, such that post-treatment LDL carried less cholesterol and HDL more cholesterol on a percentage basis than found in pre-treatment values. In the light of current concepts of atherogenicity these alterations are of interest and potentially of considerable value.