Abstract： Objective To detect HLA-DRB1(DR1-10) alleles in 5 families with multi-case rheumatic diseases, and to study the possible influence of DRB1 genes in the pathogenesis of rheumatic diseases.Methods Sequence-Specific Primer PCR (PCR-SSP)method was used to examine HLA-DRB1 alleles. Totally 36 members of 5 families and 166 healthy people were involved in this study. The results were assesed by Chi-square test.Results The HLA-DRB1 allele frequency in the patients and their relatives was similiar. No significant difference was found. But DR4 allele frequency in the patients (90.9%) and their relatives (68%) was much higher than that in normal controls (16.8%) and the difference was statistically significant (P<0.0001). In family 4, two RA patients have different DRB1 alleles, while in family 5, two patients have the same DRB1 alleles, one developed SLE and the other developed RA.Conclusions DR4 is closely related to rheumatoid arthritis. The nelatives of RA patients may be at greater risk to develop RA than individuals without family history. Some patients had the same DRB1 allele but developed different rheumatic diseases. This suggested that there might be some common pathways in genetic predisposing of rheumatic diseases. On the other hand, only a few patients with the same DRB1 allele developed rheumatic diseases during their life, so other factors besides DRB1 gene might also be involved in the pathogenesis of rheumatic diseases.