The effects of danazol on leukocyte activation in vitro were compared with those of other known immunosuppressive steroids. Danazol at a concentration of 10(-6) M, the systemic level in women taking 600 mg/day, significantly inhibited lymphocyte proliferation in cultures activated by T-cell mitogens (Concanavalin A and phytohemagglutinin) and allogeneic mixed lymphocyte culture (MLC). Comparable immunosuppressive effects were achieved in these assay systems with dexamethasone at a concentration of 10(-8) M, and with cortisol and progesterone at a concentration of 10(-6) M. Physiologic concentrations of estradiol and testosterone did not significantly affect these immunologic test systems. These studies provide evidence that danazol is immunosuppressive. It is possible that immunosuppressive effects contribute to the efficacy of this drug in the treatment of endometriosis and autoimmune disorders.