Growing female rats were fed diets containing either corn oil (CO) or cottonseed oil (CSO) to determine if the previously reported lowering effect of CSO versus CO on serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) was sex specific and to compare the effect of these two oils on serum and tissue concentrations of RRR-alpha-tocopherol (alpha-T) and RRR-gamma-tocopherol (gamma-T), the two major tocopherols in these oils. In a 4-week study, groups of rats (n = 10 each) were fed diets containing 100 g/kg of either CO or CSO. TC was lower for group CSO than group CO. Serum concentrations of HDL-C, non-HDL-C, triglycerides (TGs), as well as the TC/ HDL-C ratio and the hepatic concentrations of cholesterol and TGs, were unaffected by diet. For serum and liver, between-group differences were noted for the concentrations of alpha-T (where values were higher for group CSO) and gamma-T (where values were lower for group CSO). These differences reflected differences between the oils in their concentrations of these tocopherols. Thus, CSO has a lowering effect on TC for both sexes, but on HDL-C for male animals only; replacement of CO with CSO results in changes in tocopherol status.