It has been proposed that superantigens are involved in the pathogenesis of autoimmune diseases. To test the possibility of superantigens inducing arthritis in naive mice, V β 8-reactive superantigen staphylococcal enterotoxin B (SEB) was injected into naive mice. We used female DBA/1 mice, because they were susceptible to collagen-induced arthritis (CIA), in which the pathogenic T cells were supposed to preferentially use limited V β s of T cell receptors including V β 8. Mild monoarthritis developed in uninjected hindlimbs of mice administered with SEB in higher frequency (an average incidence of 24%) than the control phosphate-buffered saline-injected mice (4.2%). Autoimmune responses in mice administered with SEB were compared with those in mice developing CIA. However, activation of type II collagen (IIC)-reactive T cells was not detected in SEB-injected mice. Production of autoantibodies, anti-IIC antibody and rheumatoid factor was also undetected. Although exact mechanisms of pathogenesis of this arthritis remain to be known, V β 8 + T cells were activated for a long period and the unresponsiveness of V β 8 + T cells was not detected in this strain. From these results, we discuss the pathogenesis of arthritis induced by SEB and the possibility that superantigen may play a role in the induction of autoimmune diseases.