The hypolipidemic properties of ethyl 6-chlorochroman-2-carboxylate (II), ethyl 6-phenylchroman-2-carboxylate (III) and ethyl 6-cyclohexylchroman-2-carboxylate (IV) were compared to clofibrate (I) in fasted normolipidemic rats. The chroman analog II, like its parent compound, clofibrate, reduced serum and alpha-lipoprotein cholesterol concentrations. Although analog III had no effect on serum cholesterol, it caused a slight elevation of alpha-lipoprotein cholesterol concentration. Serum free cholesterol was increased and LCAT activity was reduced in clofibrate-treated rats. The hypolipidemic agents had no consistent effect on liver lipid concentrations and liver microsomal HMG-CoA reductase activity. In addition, we have shown that drug efficacies varied directly with seasonal variations in serum lipid concentrations.