An analysis of 89 male sibling pairs from multicase rheumatoid arthritis families demonstrated an association between HLA and serum testosterone levels. In sibling pairs that were haplotype identical, the mean inter-pair difference in testosterone level expressed as a log ratio was significantly less than sibling pairs sharing neither haplotype (p = 0.03). This difference was independent of the RA status of the pairs. These results suggest the presence of a gene(s) controlling testosterone levels linked to the Major Histocompatibility Complex (MHC) on chromosome 6. These findings may aid understanding of the roles of HLA antigens and sex hormones in the susceptibility to RA and other autoimmune disease.