Differences in lipoprotein(a) [Lp(a)] levels across populations have been described and blacks are known to have higher Lp(a) values compared to whites. However, environmental factors which influence Lp(a) levels have been difficult to identify. We took advantage of the large environmental contrast which exists against a common genetic background between U.S. and Nigerian blacks to examine the relationship between Lp(a) and apolipoprotein(a) magnitude of apo(a) isoforms. Although the distribution of Lp(a) and apo(a) isoforms was nearly Gaussian in both populations, mean serum Lp(a) values were significantly higher in the United States than in Nigeria (20.5 vs. 12.7 mg/dl; P = 0.0001) and U.S. blacks had a higher frequency of the large molecular weight isoforms compared to Nigerians. Similar trends in the relationship between apo(a) isoform and Lp(a) concentration were seen in both populations; however, the magnitude of the effect was different. Compared to the Nigerians, U.S. blacks had significantly higher mean Lp(a) values for the same apo(a) isoform. The association of Lp(a) with low density lipoprotein-cholesterol (LDL-C) level was not significant after correcting for the contribution of Lp(a) cholesterol to LDL-C in both populations. Surprisingly, the association between Lp(a) and total-C remained significant (r = 0.20, P = 0.04) after similar correction for the contribution of Lp(a) cholesterol in the U.S. sample. Understanding the relationship between other factors including lifestyle characteristics capable of influencing total-C may help explain the unusually high Lp(a) level observed in this U.S. population.