Polymorphisms in genes encoding transporters associated with antigen processing (TAP) have been associated with heterogeneity of disease progression in HIV-1-infected homosexual men. In our recent AIDS-related studies of cohorts from Rwanda and Zambia, four new polymorphic sites in the TAP2 coding region were detected by single-strand conformation polymorphism (SSCP) and confirmed by bi-directional nucleotide sequencing and restriction enzyme digestion. The first, a substitution of Thr (GCC) for Ala (ACC) at codon position 374 in exon 5, was found in about 13% of Rwandans and Zambians (n=213). The remaining 3 new polymorphisms were seen in the 7th exon with changes of 458Thr-ACG to ACA, 466Gly-GGG to GGA, and 467Val-GTT to Ile-ATT, respectively These 3 variants occurred exclusively on the same chromosome and appeared to have arisen together from the 374Thr-bearing allele. Analyses of the relationship between the 374Thr-467Ile segment and the nearby markers in DQB1 and DRB1 suggested the existence of a unique extended haplotype related to these newly identified variants.