Therapeutic trials with mizoribine (MZR), an imidazole nucleoside immunosuppressant, on experimental lupus nephropathy of NZB/W F1 mice resulted in the following. The MZR treatment, 20 mg per kilogram of body weight every other day, starting at 14 weeks of age, caused a significantly prolonged survival time of mice with a mean life span of 54.3 +/- 4.2 weeks, compared with the untreated controls, who had a mean survival time of 38.1 +/- 2.9 weeks (P less than 0.01). In addition, MZR suppressed the elevation of serum anti-DNA antibody titers, the spontaneous development of splenomegaly, and the histological development and progression of glomerulonephritis observed in untreated animals. Although no definite explanation is available at present to explain how MZR caused decreased anti-DNA antibody production and delay in the development of glomerulonephritis in these animals, it is suggested that it acts by directly suppressing the hyperfunctioning B cells of lupus mice. MZR may prove to be a promising immunosuppressant for the treatment of human lupus, in view of its lesser side effects such as bone marrow suppression or hepatotoxicity.