Evaluation of human leukocyte antigen (HLA) class I and class II genes was performed on patients from China with Schistosomiasis japonica. Patients were categorized as grade 0 (n=44), grade I (n=81), grade II (n=99), or grade III (n=6) based on increasing severity of hepatic fibrosis due to repeated Schistosoma japonicum infections. These results show that the HLA-DRB1*1101-DQA1*0501-DQB1*0301 (Pc<0.02) and HLA-DRB1*1501-DRB5*0101 (Pc<0.02) haplotypes are associated with protection and susceptibility to grade I fibrosis, respectively, and that the HLA-DPA1*0103 -DPB1*0201 haplotype (Pc<0.02) is associated with protection from both grade II and III severe fibrosis. There was no association between HLA-B DNA haplotypes and the disease. These findings indicate that the HLA-class II molecules play a role in preventing or promoting fibrotic liver change after deposition with Schistosome eggs. Moreover, a tendency was observed within the HLA class II genes for the HLA-DR-DQ alleles to be associated with protection against early changes in liver fibrosis, whereas HLA-DP alleles were associated with protection from the late phase of fibrosis or severe hepatosplenic schistosomiasis.