Lipoprotein(a) is an atherogenic lipoprotein whose function and plasma concentration reflect the structure and regulation of the apolipoprotein(a) gene. Apolipoprotein(a) is a close homologue of plasminogen, and their genes are tightly linked on chromosome 6. To further characterize these genes, we analyzed overlapping human genomic yeast artificial chromosome clones, which revealed a cluster of four highly homologous genes encoding apolipoprotein(a), plasminogen, and two apolipoprotein(a)-related genes (rg) or pseudogenes. Hybridization analysis and reverse transcriptase polymerase chain reaction showed that one of these novel genes, designated apolipoprotein(a)rg-C, has a domain structure similar to apolipoprotein(a) and is transcribed in human liver. Three additional homologues designated as plasminogen-related genes are shown to be unlinked to this gene cluster and reside on chromosomes 2 and 4.