Postmenopausal hypercholesterolemic women are at risk for cardiovascular disease and are encouraged to follow low-fat (LF) (< or = 30% energy) diets. However, these diets may have undesirable effects on high density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apo A-I) and triglycerides, whereas diets high in monounsaturated fats do not. Twenty postmenopausal hypercholesterolemic women previously consuming high-fat diets (34% energy) were placed on a low fat-monounsaturated rich diet (LFMR: 26%, 14% energy, respectively) for 6 men. Sixteen women already eating LF diets (24% energy) were also followed to monitor variations in serum lipids due to seasonal variations. Twenty-five women successfully completed the study (LFMR = 12, LF = 13). Serum cholesterol decreased 10% (264 to 238 mg/dL, P < or = 0.01) and low density lipoprotein cholesterol (LDL-C) decreased 12% (182 to 161 mg/dL, P < or = 0.01) in the LFMR group, but did not change in the LF group. The reduction in serum cholesterol in the LFMR group was greater than estimated by predictive formulas. Serum triglycerides and apo A-I did not change in the LFMR group. A modest decrease in HDL-C, HDL3-C, and apolipoprotein B (apo B) occurred in both groups, but only the LFMR group showed a trend toward beneficial changes in LDL-C/HDL-C and apo A-Vapo B ratios. Overall, the LFMR diet was well tolerated and resulted in an improved serum lipid and apolipoprotein profile.