Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from high-density lipoprotein (HDL) to apolipoprotein (apo)B-containing lipoproteins, whereby it potentially regulates steady-state concentrations of HDL-cholesterol (HDL-C), as well as low-density lipoprotein-cholesterol (LDL-C). We performed a multicenter trial to assess the association of CETP activity with plasma lipoprotein levels in 591 Japanese subjects. Women had significantly higher CETP activity (15%) and mass (24%) compared to men. For both genders CETP activity was negatively correlated with HDL-C and HDL(2)-C, but positively correlated with LDL-C. B2 allele frequency in TaqIB polymorphism was 40%, with no gender difference. TaqIB genotypes were significantly associated with CETP activity and HDL-C level (both P <.001). B1B1 had the highest CETP activity and the lowest HDL-C concentrations, whereas B2B2 had the lowest CETP activity and the highest HDL-C concentrations. However, no statistically significant differences in triglycerides (TG) or LDL-C were observed across TaqIB genotypes. Multivariate analysis revealed that determinants of HDL-C were age, gender, body mass index (BMI), smoking, alcohol intake, exercise, CETP activity, and TG, and for LDL-C were BMI, age, and CETP. These data demonstrate that CETP activity is a significant determinant of HDL-C and LDL-C levels and that TaqIB CETP gene polymorphism affects CETP activity and HDL-C level in Japanese population examined.