Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglyceride between high density lipoprotein (HDL) and very low density lipoprotein. The B2 allele of the TaqIB polymorphism located in the first intron of the CETP gene occurs with an allele frequency of about 0.40 in Caucasians and is associated with decreased CETP levels and activity and with higher HDL-cholesterol (HDL-C) levels in this racial group. We hypothesized that the higher levels of HDL-C seen in African Americans compared with Caucasians could be in part explained by a higher frequency of the TaqI B2 allele. We determined the distribution of this polymorphism in a total of 395 African Americans and 362 Caucasian ascertained as two independent cohorts: one of healthy volunteers (NORM) and the other of patients undergoing cardiac catheterization (CATH). Of the 244 NORM-African Americans studied, 56% were B1B1, 37% B1B2 and 7% B2B2, compared with the 224 NORM-Caucasians of which 33% were B1B1, 45% B1B2 and 22% B2B2. In the CATH-African American group (n=151) 51% were B1B1, 41% B1B2 and 8% B2B2 compared with 35% CATH-Caucasians B1B1, 54% B1B2 and 11% B2B2. The frequency of the B2 allele in the Caucasian subjects in both cohorts was similar to that reported in the literature. The frequency of the B2 allele was significantly lower in African Americans than in Caucasians in the NORM group (0.26 vs 0.44; chi(2)=36.5, P<0.001) and in the CATH group (0.28 vs 0.38, chi(2)=4.7, P=0.01). Carriers of the B2 allele had higher HDL-C levels compared with B1B1 subjects in Caucasians (NORM: 57 vs 53 mg/dl, P=0.035; CATH: 47 vs 42 mg/dl, P=0.049) and in CATH-African Americans (48 vs 43 mg/dl, P=0.028), but not in NORM-African Americans (55 vs 54 mg/dl, P=0.494). There were no other significant associations between this polymorphism and other lipids and lipoproteins in the subjects studied. These results suggest that, in contrast to our hypothesis, the B2 allele of the TaqIB polymorphism is less frequent in African Americans compared with Caucasians and that this polymorphism is unlikely to contribute to the higher levels of HDL-C reported in the African American population.