Five‐month‐old female NZB/W mice were treated with daily injections of azathioprine, cyclophosphamide or methylprednisolone. Treatment was continued for 2 or 3 months at different dosages. Renal histology, proteinuria, antibodies to DNA and survival were studied. All drugs were found to modify the disease favorably. At low doses (1.5 mg/kg/day) azathioprine was most effective. Cyclophosphamide was superior at higher doses (4.5 mg/kg/day). Different two‐drug combinations were also compared. The combination of cyclophosphamide plus methylprednisolone was most effective. Combined therapy increased survival without increasing toxicity.