Genotypes at five previously described polymorphic sites at the apolipoprotein(a) gene locus have been determined for the members of 27 families as well as for unrelated white Caucasian and Asian-Indian subjects, and their relationship with isoform size and plasma lipoprotein(a) concentrations investigated. There was strong linkage disequilibrium between sites at the 5'-region of the gene and also between this region and a site in the coding sequence for Kringle 4-37 on the other side of the polymorphic Kringle 4 repeat region. There was no evidence that changes at any of the sites had any direct effect upon lipoprotein(a) concentration. However, certain haplotypes were present almost exclusively on apolipoprotein(a) alleles within a restricted range of sizes and associated lipoprotein(a) concentrations. After correcting for the effect of allele size, there were clear differences between the lipoprotein(a) concentrations associated with alleles of different haplotypes, suggesting that there may be genetically distinct groups of apolipoprotein alleles of different size and different levels of expression. Factors that regulate expression apparently exchange at a rate similar to the rate of change of Kringle 4 repeat number.