CD23 is a low-affinity receptor for immunoglobulin E (IgE) expressed by a variety of haematopoietic cells. Proteolytic cleavage of the transmembrane receptor generates soluble forms, which can be detected in biological fluids. CD23 regulates many functional aspects of immune cells, both in its cell-associated and soluble forms. In view of the increased levels of CD23 in rheumatoid arthritis, we have studied the effect of neutralizing CD23 in type II collagen-induced arthritis in mice, a model for human rheumatoid arthritis. Successful disease modulation is achieved by treatment of arthritic DBA/1 mice with either polyclonal or monoclonal antibodies to mouse CD23. Treated mice show a dose-related amelioration of arthritis with significantly reduced clinical scores and number of affected paws. This improvement in clinical severity is confirmed by histological examination of the arthritic paws. A marked decrease in cellular infiltration of the synovial sublining layer and limited destruction of cartilage and bone is evident in animals treated with therapeutic doses of anti-CD23 antibody. These findings demonstrate the involvement of CD23 in a mouse model of human rheumatoid arthritis.