The frequency and HLA-A allelic associations of a HERVK9 DNA structural polymorphism located in close proximity to the highly polymorphic HLA-A gene within the major histocompatibility complex (MHC) genomic region were determined in Japanese, African Americans, and Australian Caucasians to better understand its human population evolutionary history. The HERVK9 insertion or deletion was detected as a 3' LTR or a solo LTR, respectively, by separate PCR assays. The average insertion frequency of the HERVK9.HG was significantly different (P < 1.083e(-6)) between the Japanese (0.59) and the African Americans (0.34) or Australian Caucasians (0.37). LD analysis predicted a highly significant (P < 1.0e(-5)) linkage between the HLA-A and HERVK9 alleles, probably as a result of hitchhiking (linkage). Evolutionary time estimates of the solo, 5' and 3' LTR nucleotide sequence divergences suggest that the HERVK9 was inserted 17.3 MYA with the first structural deletion occurring 15.1 MYA. The LTR/HLA-A haplotypes appear to have been formed mostly during the past 3.9 MY. The HERVK9 insertion and deletion, detected by a simple and economical PCR method, is an informative genetic and evolutionary marker for the study of HLA-A haplotype variations, human migration, the origins of contemporary populations, and the possibility of disease associations.