Recent evidence indicates that the HLA system might, in some way, regulate androgen concentrations. Male patients affected by rheumatoid arthritis have been shown to possess low serum testosterone levels associated with a particular HLA haplotype. Furthermore, androgen receptors have been recently described in macrophage-like synoviocytes that are HLA-DR positive. Since androgens generally are immunosuppressive, the possible mechanisms of their action in rheumatoid arthritis are here reviewed and discussed. It has now become evident that the well known relationship between sex hormones and the immune system is more complex than was previously suspected.