Investigators from this laboratory have been studying sex hormones in normal and autoimmune mice for the past 10 years. We have found that immune responses to DNA are influenced by sex hormones. Androgens reduce and estrogens increase both spontaneous and immunization‐induced antibodies to single‐stranded DNA in NZB x NZW, NZB x C3H, NZB x CBA, NZB x DBA mice. Treatment of female NZB/W mice with testosterone or 5 α dihydrotestosterone retards the progress of autoimmunity. Castration is not necessary for this effect. In contrast, danazol has no favorable effect on the disease process. Estrogens cause a marked acceleration of autoimmunity and a reduction in thymus weight. During the course of these studies, we found that a number of problems or variables arise in studying sex hormone effects, including: 1) X‐linked genes, 2) metabolism of testosterone to estrogens, 3) dose of hormone, 4) age at which administration is initiated, 5) differential effects of sex hormones on different autoantibodies and various immune responses.