SummaryMutations in the human CC chemokine receptor 5 (CCR5) gene may alter the expression or function of the protein product, thereby altering chemokine binding/signalling or human immunodeficiency virus type 1 (HIV‐1) infection of the cells that normally express CCR5 protein. We performed a systematic survey of natural sequence variations in an 8.1‐kb region of the entire CCR5 gene as well as CCR2V64I in 50 Japanese subjects and evaluated the effects of those variations on CCR5 promoter activity. We also analysed CCR5 promoters and CCR2V64I in 80 more Japanese and 186 Thais. There was no 32‐bp deletion observed in Caucasians, but two types of non‐synonymous substitutions were found in CCR5 genes of Japanese. Our results showed several novel characteristics of the CCR2‐CCR5 haplotype structure that were not reported from studies on Caucasians and African‐Americans. Specifically, we were able to show that the G allele at position –2852 from the CCR5 open reading frame in Japanese and Thais is the representative of the CCR5 promoter haplotype that was reported to be associated with rapid progression to acquired immune deficiency syndrome (AIDS) in HIV‐1‐infected individuals. Furthermore, nearly all non‐synonymous polymorphisms in Japanese CCR5 occurred in haplotypes with elevated promoter activity. We thus hypothesized that there was a certain selective pressure favouring low levels of CCR5 expression during human evolution.