Genetic polymorphism at the apolipoprotein(a) structural locus was investigated in 203 American blacks using a high-resolution SDS-agarose electrophoresis method followed by immunoblotting, and the gene frequency data were compared with a previously screened American white sample using the same method. Between the two samples, a total of 27 discrete APO(a) allelic isoforms have been documented; of these, 24 were common to both groups. Of the 203 blacks screened, APO(a) immunoreactive isoforms were detected in 201, with a total of 101 distinct phenotypes (67 (33%) single-banded and 134 (67%) double-banded). A similar level of gene diversity was observed at the APO(a) locus in blacks (93%) and whites (94%). Despite having a similar number of alleles and a similar level of gene diversity, the frequencies of some APO(a) alleles were significantly different between blacks and whites. Overall, the frequencies of large-size APO(a) alleles, associated with lower LP(a) levels, were significantly lower (P < 0.0001), while the frequencies of medium-size APO(a) alleles, associated with intermediate LP(a) levels, were significantly higher (P < 0.0001) in blacks than in whites. However, the frequencies of small-size alleles, associated with higher LP(a) levels, were comparable between the two race groups. These data indicate that the observed differences in mean LP(a) levels between whites and blacks may be accounted for by the size variation at the APO(a) structural locus.