The aim of this study was to compare the effects of a diet enriched with monounsaturated (MUFAs) with one enriched with polyunsaturated (PUFAs) fatty acids on the serum lipoprotein composition in patients with hyperlipidemia. A new model for conducting controlled dietary treatment studies in free-living hyperlipidemic patients was tested. Twenty-six patients with an average age of 51 y participated in a crossover study during two consecutive 3.5-wk treatment periods. The mean serum cholesterol and LDL cholesterol decreased by 17% and 19%, respectively, on the MUFA diet. The corresponding figures on the PUFA diet were 19% and 23%, respectively. The HDL-cholesterol concentration was significantly decreased after both dietary periods. No significant differences in any of the variables studied were found between the diets. It is concluded that MUFAs and PUFAs, within a diet with a restricted content of saturated fat and total fat, are interchangeable with regard to lipid-lowering effects among free-living hyperlipidemic patients.