Lipoprotein lipase (LPL) plays a crucial role in plasma lipoprotein processing by catalyzing the hydrolysis of core triglycerides of chylomicrons and very low density lipoproteins. Several polymorphic restriction sites have been reported in the LPL gene, including those identified by the enzymes HindIII and PvuII. We have determined the HindIII and PvuII polymorphisms in diabetic (D) and non-diabetic (ND) Hispanics (D = 195; ND = 384) and non-Hispanic Whites (D = 76; ND = 539) from the San Luis Valley, Colorado. Both polymorphisms showed comparable gene frequencies between diabetics and non-diabetics, and between the two ethnic groups. The HindIII and PvuII polymorphisms were in strong linkage disequilibrium in both Hispanics and non-Hispanic Whites (P < 0.001). We estimated whether the two DNA polymorphisms have significant impact in determining interindividual differences in plasma levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, and fasting insulin. Plasma triglyceride levels varied significantly among the HindIII genotypes in the normoglycemic sample. There was a clear gene dosage effect among the three HindIII genotypes, with the (-/-) genotype having the lowest and the (+/+) genotype having the highest triglyceride levels; these levels were intermediate in the (+/-) genotype. The average effect of the (-) allele of the HindIII polymorphism was to lower triglycerides by 12.85 mg/dl in non-Hispanic White males, 8.06 mg/dl in non-Hispanic White females, 10.91 mg/dl in Hispanic males, and 12.47 mg/dl in Hispanic females. The HindIII polymorphism also showed a significant association with HDL-cholesterol levels in the normoglycemic sample.(ABSTRACT TRUNCATED AT 250 WORDS)