Some experimental arthritic diseases can be prevented by treatment with anti-CD4 MoAbs. Trials with ongoing disease have not been successful so far. The aim of this study was to ascertain whether W3/25 could reverse adjuvant arthritis (AA), when beginning treatment on day 14, i.e. when the disease was established. Moreover, one group of animals treated with the anti-CD4 MoAb received OX8 MoAb at the same time, thus depleting CD8+ cells from circulation. During treatment with W3/25, a strong amelioration of inflammatory signals were observed, as assessed by means of paw volume increase and arthritic score. However, when treatment stopped, a rebound to arthritis signals occurred. The parallel depletion of CD8+ cells did not modify these effects, thus the combined treatment W3/25 + OX8 gave the same amelioration as treatment with W3/25 alone. These findings indicate that CD4+ cells play an important role in perpetuating rat AA. Moreover, CD8+ cells do not seem to have a regulatory role int he CD4+ cells responsible for the inflammatory response.