We present results from an association study between RFLPs in the lipoprotein lipase (LPL) gene and lipid and insulin levels. The study population consisted of 102 Hispanic men and 97 Hispanic women. The subjects were genotyped for two previously reported RFLPs detected with the restriction enzymes HindIII and PvuII. The frequencies of the RFLPs in the Hispanic population are similar to those seen in other Caucasian populations. Strong linkage disequilibrium was detected between the sites in Hispanics. Genotypes were used separately in analyses of variance with fasting serum triglycerides, total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, HDL2/HDL3-cholesterol, and insulin levels, as well as two measures of adiposity: waist-hip ratio and body mass index. Men and women were analyzed separately. Mean fasting insulin levels of the LPL PvuII genotypes were significantly different from each other in Hispanic men. The mean fasting insulin level of men who were homozygous for the presence of the PvuII site (+/+) was 9.20 ± 0.24 μunits/ml, men who were heterozygous had a mean level of 10.54 ± 0.20 μunits/ml, and men who were homozygous for the absence of the site (-/-) had a mean of 12.91 ± 0.30 μunits/ml. This effect was not seen in Hispanic women. These results suggest that the regulation of LPL by insulin may be different in Hispanics with different LPL PvuII genotypes. © 1993 Wiley-Liss, Inc.