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 (delta=0.67. P=0.0001), compared to delta=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.