Results of allogeneic bone marrow transplantation (BMT) are still impaired due mainly to acute graft-versus-host disease (GVHD). Successful T cell depletion may abolish GVHD but causes increased rates of rejection and relapse. In vivo blocking of the CD25 receptor on T cells induces efficient and selective immunosuppression. We present results of a pilot trial studying the use of a CD25 MoAb (33B3.1) to prevent acute GVHD after allogeneic BMT. Fifteen patients were included in the study; 14 had a fully HLA matched sibling donor. In association with short methotrexate and cyclosporin A post-graft immunosuppression, the patients received 10 mg of 33B3.1 monoclonal antibody daily according to three successive schedules to study toxicity on marrow graft. No major adverse clinical experiences occurred. Engraftment was not delayed; after 4 months, full chimerism was documented in 14/15 studied patients. No human anti-rat antibody was detected during treatment period. No GVHD occurred during the period of antibody administration. Two patients relapsed; seven are alive and well with a median follow-up of 650 days. This study justifies a prospective controlled study to determine the real impact of 33B3.1 on GVHD prophylaxis.