Major histocompatibility complex (MHC) class II locus DRB was investigated by single-strand conformation polymorphism analysis (SSCP) and sequence analysis in the endemic South African antelope, Damaliscus pygargus, of which there are two subspecies. Greater polymorphism was found in the blesbok (D. p. phillipsi) subspecies (n = 44; 22 alleles) than in the bontebok (D. p. pygargus) subspecies (n = 45; 6 alleles). Erosion of allelic diversity in bontebok was most likely the result of two severe bottleneck events caused by hunting pressure and parasitic infection. A majority of the polymorphism observed was found within the peptide binding region (PBR) where dN/dS ratios were higher than for the non-PBR region. This, and the apparent trans-species relationship among alleles in a bovid phylogeny, suggest the evolution of diversity by heterosis or frequency-dependent selection.