We have investigated the effects of recombinant murine interferon-gamma (rIFN-gamma) on type II collagen-induced arthritis (CA) in DBA/l mice. Therapeutic as well as prophylactic treatment with subcutaneous rIFN-gamma, at 10(5) U/mouse six times a week, inhibited the development of CA without any obvious side effects. The accompanying suppression of anti-CII antibody responses may partly explain the inhibition of CA by rIFN-gamma. The possible role of the anti-inflammatory effect of systemic IFN-gamma in the inhibition of CA is discussed.