The course of hepatitis B virus (HBV) infection may be influenced by the host immune response. A prospective study was carried out in ninety-eight subjects (mean age = 23 years) HBs antigens carriers of hepatitis B and living in Dakar, Senegal. We analysed the HLA-A, -B, and C antigens distribution compared to that one of a control (HBs negative) healthy senegalese population (n = 96) living in Dielmo village where a longitudinal study was set-up since 1990. The HLA class I typing was performed by microlymphocytotoxicity assays. The most frequent HLA-A, -B, -C antigens found were: locus A: A23 (33.6%), A2 (25%), A30 (25%), locus B: B8 (31%), B7 (16.3%), B58 (11.9%), B35 (11%), B49 (11%), B53 (10.8%) and locus C: Cw7 (39.1%), Cw17 (39.1%), Cw3 (36.9%), Cw4 (36.6%). Significant differences (P < 0.001) were found between the donors and the control group for the following HLA antigens: A1, A23, B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (p < 0.01) between positive and negative HBe donors for HLA-A1 allele with an odds ratio of 6.25. All the donors carrying the HLA haplotype: A1-B8-Cw7 (11.5%) were positive in HBe antigen. HLA: B8-Cw7 haplotype (detected in 8.5% of positive donors) seems to be likely associated with a liver cancer according to many reports. An adequate follow-up should be set-up for positive HBe subjects carrying a susceptible HLA type.