We have analysed the HLA allele distributions in unrelated Namibian Khoi and San and South African Xhosa and mixed-ancestry (so-called Cape coloured) populations. The allelic specificities of the DRB1, DQA1, DQB1 and DPB1 loci were determined. We found loss of allelic diversity and predominance of certain alleles to be more pronounced in the San than in the Khoi. By contrast, the Xhosa indicated wide allelic diversity especially at the DRB1 and DPB1 loci. We found evidence that the Caucasoids may have been derived from an early migration wave, whereas African blacks arose from a later migration wave of an ancestral population pre-dating ethnic diversity. Frequencies in the Xhosa for the DRB10302, 1101, 1302 and 1304 alleles revealed clinal variation in a north-south direction across the African continent. For the DRB1, DQA1, DQB1 haplotypes there was greater variation in the Khoi than in the San, in whom certain haplotypes predominated. We found 13 previously unreported haplotypes. In Xhosa we found 30 different DRB1, DQA1, DQB1 haplotypes. Allele and haplotype characteristics and frequencies in the South African mixed-ancestry population were mostly intermediate between those found in Xhosa and reported for Caucasoids, and three possible ancestral southern African DRB1, DQB1, DPB1 haplotypes were found. We discuss the implications of our findings for organ donor transplantation in Xhosa and in the South African mixed-ancestry population
