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The lipoprotein lipase (LPL) promoter -93T/G transition has previously been reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant has been shown to have a Tg-raising effect. These two variants were studied in 66 healthy subjects of Hispanic and 42 subjects of African-American origin, who had participated in a study of postprandial lipemia. While the allele frequency of the -93G was significantly different in the Hispanics and African Americans (0.09: 95% CI 0.04–0.13 and 0.28: 95% CI 0.19–0.38; P = 0.0001, respectively), the N9 allele frequency was not different (0.06: 95% CI 0.02–0.1 and 0.05: 95% CI 0.002–0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was highly significant in Hispanics (Δ = 0.67. P = 0.0001), compared to Δ = 0.09 (NS) in African-Americans. In the combined group, compared to individuals with the common genotype (TT/DD; n = 71) with fasting plasma Tg of 1.34 (±4.5% SEM) mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n = 25) had significantly lower plasma Tg levels of 1.08 (±10% SEM) mmol/l (P < 0.02). After the fat meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl palmitate concentration at 5 hrs was significantly lower in G/D carriers than TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was not significant in this group. Thus carriers of the G/D haplotype have lower fasting plasma Tg and reduced alimentary lipemia. This allele may be associated with reduced risk of coronary artery disease.—Talmud, P. J., S. Hall, S. Holleran, R. Ramakrishnan, H. N. Ginsberg, and S.E. Humphries. LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics. J. Lipid Res. 1998. 39: 1189–1196.