To study the immunoreactivity genes in a heterogeneous human population needs a large number of individuals. Associations between HLA antigens and immunoresponse to viral or bacterial antigens have been studied with controversial results. As a homogeneous population, the MHC class I, II and III allele distribution was studied in 153 end-stage renal disease patients (ESRD, average duration of renal replacement: 8.2 + 5.1 years) immunized with a recombinant hepatitis B vaccine in accordance to the standard vaccination schedule. Thirty-four patients with an antibody titre of less than 10 U/l following the last booster injection were considered as non-responders while 119 patients with antibody titre equal to or more than 10 U/l were considered as responders. The responder group was divided into two subgroups: low responders (antibody titre: < or = 1000 U/l) and high responders (antibody titre: > 1000 U/1). Marked differences were observed between responders and non-responders in the occurrence of carriers of different MHC class I, II and III alleles. Homozygotes for HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 were found almost exclusively in the non-responder group and significantly more heterozygotes for these alleles were found in the non-responder group compared to the responders. Similar albeit less marked differences were found in the frequency of some MHC class III alleles (C4A*6, C4A*QO, Bf*F, Bf*S0.7). Within the responder group, carriers of HLA-A2, HLA-B7 and HLA-DR4 were found to be clustered in the low responder sub-group whereas carriers of HLA-A1, HLA-B27, HLA-Cw2, C4A*6 and Bf*F were observed more frequently in the group of high responders. Similar differences were found with extended haplotypes as well. For example, the extended haplotypes HLA-A1, B8, BfS, C4AQO, C4B1, DR3, DQ2 and HLA-A1, B8, BfF, C4A6, C4B2, DR3, DQ2 were present in nine of 34 cases of non-responders but only in one of 119 case of responders (P < 0.000001). These observations indicate that the presence or absence of certain MHC alleles even in heterozygous form determine the responsiveness to hepatitis B vaccination in end-stage renal disease patients, and among responders, the intensity of antibody response is also markedly influence by immunogenetic factors.