The effect of immunosuppression with cyclophosphamide was assessed in 200 male and female Walter and Eliza Hall Institute outbred mice which are known to develop antinuclear antibody (ANA). Their longevity and the incidence of ANA were studied in comparison with controls. In females, life-span was longer despite a higher age-related incidence of ANA. Cyclophosphamide significantly delayed the development of ANA in both sexes; despite this, life-span was decreased. This is in contrast to what occurs in the highly autoimmune NZB/NZW F1 hybrid mouse. Thus, in weakly autoimmune mice the toxic effects of cyclophosphamide outweighed any benefit resulting from suppression of antinuclear autoantibodies.