Female MRL/lpr mice develop lesions closely resembling human systemic lupus, and therefore can serve as models in order to examine the efficacy of immunosuppressive agents. The present study was designed to evaluate the efficacy of the combination of deoxyspergualin with prednisolone compared with each alone in 13-week-old female MRL/lpr mice. After the onset of lymphadenopathy, splenomegaly, and the elevation of plasma autoantibodies, deoxyspergualin alone or prednisolone alone was effective. An immunosuppressive regimen of deoxyspergualin combined with prednisolone was demonstrated to be superior to each single therapy concerning the amelioration of advanced disease in the MRL/lpr mice without increasing toxicity.