Ten patients (6 women and 4 men), with a group mean age of 65 years, defined as severe and with a mean follow-up period of 9 years and refractory to conventional treatments, were treated with monoclonal anti-CD4 antibodies in an open study. The monoclonal antibodies, of murine origin, were administered by intravenous route for ten consecutive days at a dose of 10 mg (1 patient), 15 mg (2 patients) or 20 mg (7 patients). Local and systemic tolerability were excellent. Clinical improvement was rapid (pain, morning stiffness, Ritchie index, p = 0.005 between D0 and D15), as was the paraclinical improvement (C-reacting protein, p = 0.008), although without achieving complete remission. The outcome revealed that the effect was more prolonged in patients treated with 20 mg per day than in the others, suggesting a dose-effect relationship. The improvement obtained may persist for more than 9 months in some patients. No significant change in immunological parameters was found at the end of the treatment (lymphocyte populations, immunoglobulins, complement). Only 2 out of 10 patients developed anti-mouse antibodies. As a result of its excellent tolerability and rapid effectiveness, this antibody appears to offer fresh therapeutic prospects in rheumatoid arthritis.