This study examines the effect of mizoribine (MZR), an immunosuppressant, on collagen-induced arthritis in mice. DBA/1J mice, immunized on days 0 and 21 with 200 micrograms of type II collagen in complete Freund adjuvant, were treated with various doses of MZR for 12 weeks, beginning on the day after the primary immunization. MZR reduced the arthritis score in a dose-dependent fashion, showing significant suppression, even at a dose of 10 mg/kg. At doses of more than 20 mg/kg, MZR also significantly suppressed bone damage in the hind limbs. MZR significantly suppressed the delayed-type hypersensitivity response to type II collagen, but only slightly decreased anti-type II collagen antibody levels. MZR restored the L3T4+/Lyt-2+ ratio, which was increased in arthritic mice, to the level found in normal mice. These findings show that MZR suppresses collagen-induced arthritis and bone damage in mice, and suggest that the inhibitory effect of MZR is based on its suppression of cellular immunity. These results provide a theoretical basis for the clinical use of MZR in rheumatoid arthritis.