The incidence of systemic lupus erythematosus (SLE) is known to be affected by sex hormone. Patients with Klinefelter's syndrome were reported to have abnormal sex hormonal metabolism and their chronic estrogenic stimulation seems to affect the pathogenesis of SLE. Therefore, association of SLE and Klinefelter's syndrome has been considered as a clue of the effect of sex hormone on SLE. We report the first case of Klinefelter's syndrome in a patient with SLE in Korea and discuss the association of SLE with Klinefelter's syndrome.(Korean J Med 59:331-334, 2000)