Cyclophosphamide (Cy) has been demonstrated to be effective in treating autoimmune disease in NZB/NZW F1 mice. This study was designed to compare the efficacy of chlorambucil (Chlor) with that of a known effective drug (Cy) in the treatment of murine lupus. NZB/W female mice were treated with Cy, Chlor, or nothing on a once‐a‐month dosage schedule. The age of onset of proteinuria, the severity of glomerular lesions, and the median survival were compared among the three treatment groups. Cy was found to be superior to Chlor and controls in all measures.