The purpose of this study was to assess the contribution of the apolipoprotein E (apoE) polymorphism and factors, such as age and waist circumference, to variations in plasma low-density lipoprotein-cholesterol (LDL-C) response following ad libitum consumption of a diet rich in complex carbohydrates (high-CHO: 58% of energy as CHO) versus a diet rich in fat and monounsaturated fatty acids (high-MUFA: fat, 40% of energy and 22% as MUFA). Sixty-five men participated in this parallel 6- to 7-week study involving either a high-CHO or a high-MUFA diet. Fasting plasma lipid profile and anthropometry were determined at the beginning and at the end of the dietary period. The high-CHO and high-MUFA diets both induced significant (P<.01) and comparable reductions in body weight and waist circumference. These changes were associated with a significant (P<.01) and comparable decrease in LDL-C (-19% and -16%, respectively). Stepwise multiple regression analyses showed that 32% of the variation in the LDL-C response to the high-CHO diet was attributable to the apoE polymorphism (18.5%, P=.04) and waist circumference (13.5%, P=.03) indicating that men with a waist circumference greater than 100 cm and the E2 allele had the greatest reduction in plasma LDL-C after the high-CHO diet. On the other hand, in the high-MUFA group, waist circumference was the only significant contributing factor to the LDL-C response and accounted for 44.5% of its variance. In conclusion, the plasma LDL-C response to ad libitum comsumption of a high-CHO and a high-MUFA diets are not modulated to the same extent by the apoE polymorphism and waist circumference.