The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association with serum lipoprotein-lipid and apolipoprotein levels in four large samples comprising Hispanics ( n=373) and non-Hispanic Whites ( n=522) from the U.S. and Nigerian Blacks from Sokoto ( n=390) and Benin ( n=800). A total of four alleles, designated 83, 87, 91 and 95 bp, were observed. The 83 bp allele was observed at 0.4–1.1% in the two U.S. populations but was completely absent in African Blacks. Sokoto Blacks had significantly different frequencies of the 87 and 91 bp alleles compared to Hispanics ( P=0.008) and non-Hispanic Whites ( P=0.024). The frequency of the 91 bp allele was also significantly higher in Benin Blacks compared to Hispanics ( P=0.026) and non-Hispanic Whites ( P=0.054). The analysis of the relationship between the LRP polymorphism and serum lipid traits yielded some significant race and gender specific significant association for lipoprotein(a) in non-Hispanic White males ( P=0.02); HDL 2-cholesterol in Hispanic females ( P=0.03) and apolipoprotein B in Benin males ( P=0.04). We also observed an interaction between the LRP polymorphism and menopausal status for Lp(a) in Hispanic famales ( P=0.014). However, considering multiple comparisons were performed, these associations could be due to chance. Our data indicate that although the LRP tetranucleotide polymorphism exhibits inter-racial differences in its distribution, it does not appear to have a significant role in affecting serum lipid traits.