Development of autoimmune disease in female New Zealand hybrid mice was dramatically modified by classical conditioning of immunosuppression. Groups of animals received each week a solution of sodium saccharin (conditioned stimulus). One group of conditioned animals received an injection of cyclophosphamide (the unconditioned stimulus) after half of the weekly occasions when they received the saccharin solution. The rate of development of proteinuria and mortality were significantly retarded in these conditioned mice relative to untreated controls and nonconditioned animals that received unpaired treatment with saccharin and cyclophosphamide.