Sex hormones play an important role in determining the progression and severity of autoimmune diseases, but the in vivo mechanisms underlying this relation are poorly understood. The main objective of current study has been to compare the changes in neuroendocrine immune features and autoantibody profile in male patients with hypogonadotropic and hypergonadotropic hypogonadism, and to determine the relationships between sex hormones and immunologic parameters. Thirty-seven male patients with Klinefelter's syndrome and 35 men with idiopathic hypogonadotropic hypogonadism who had no history of previous hormonal therapy and 30 healthy men were recruited in the study. Serum autoantibody profile, sex hormones, and immunologic parameters were studied. In conclusion, our findings suggest that both humoral and cellular immunity is enhanced in male hypogonadism. Klinefelter's syndrome patients also had increased frequency of antiextractable nuclear antibodies and anticardiolipin antibodies positivity compared to idiopathic hypogonadotropic hypogonadism patients. It is possible that testosterone deficiency and increased levels of estradiol are primary responsible factors for this enhanced autoantibody production in Klinefelter's syndrome patients.