The microsomal triglyceride transfer protein (MTP) plays a key role in the assembly of apolipoprotein B (apoB)-containing lipoproteins. We investigated the relation between lipid profiles and a common functional polymorphism (-493G/T) of the MTP gene in a large sample of young black men in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We performed serial cross-sectional analyses on lipids of 586 black men in 5 exams over 10 years of follow-up. Total cholesterol, LDL cholesterol, and apoB levels were very similar between the GT and GG genotypes; therefore, the GT and GG genotypes were combined as 1 group when the 3 phenotypes were analyzed. The results from ANCOVA showed that the TT group (prevalence 7%) had higher levels of apoB-related lipids than did the GT+GG group: the difference in total cholesterol ranged from 2 (P=0.79) to 19 (P=0.002) mg/dL in exams 1 to 5; the difference in LDL cholesterol ranged from 10 (P=0.14) to 17 (P=0.003) mg/dL in exams 1 to 4, but in examination 5, the difference became negligible. The TT group had higher levels of apoB, measured in only 2 exams, by 6 (P=0.12) and 9 (P=0.03) mg/dL. The TT group had higher levels of triglycerides than did the TG or GG group by 3 to 34 (P=0.02 to approximately 0.003) mg/dL in all 5 exams. HDL cholesterol and apolipoprotein A-I levels were similar among the 3 genotypes. Our serial cross-sectional analyses indicated that the TT genotype was associated with higher levels of total cholesterol, LDL cholesterol, triglycerides, and apoB in young black men. The broad effect of this polymorphism on several atherogenic traits suggests that the MTP gene could be influential in atherosclerosis.