The Mandenka population is an endogamous community of about 3,000 individuals living in the Niokholo area of Eastern Senegal. Their genetic structure has previously been investigated for numerous polymorphisms, including serological markers, HLA-C and HLA class II molecular polymorphisms, mtDNA, random nuclear probes, the Y chromosome, and α- and β-globin. We report here new results obtained by high-resolution DNA typings of 2 HLA class I loci (A and B), and compare them to those found for other HLA loci. The analysis of molecular diversity at each locus reveals contrasting allelic distributions in this population: while some class II alleles are very frequent (DPB1*1701: 35%, DRB1*1304: 25%, DQB1*0301: 53%), class I allelic frequencies never exceed 20% (A*2301: 18%, B*3501: 13%, Cw*0401: 19%). Also, class I haplotype frequencies seldom reach 5%, and only a few HLA-ABC haplotypes above 3% exhibit all allelic pairs in significant linkage disequilibrium (3002-3501-0401, 0202-5801-03 and 8001-4410-0401). Finally, a significant excess of heterozygotes is detected at 2 of 3 class I loci, but not at class II. These results suggest that the HLA region has followed heterogeneous modes of evolution.