The efficacy of the rat monoclonal IgG2b antibody LO-Tact-1 specific for the human interleukin-2 (IL-2) receptor was evaluated for prophylaxis of graft-versus-host disease (GVHD) in patients who received transplants of marrow from HLA-matched sibling donors. Fifteen patients received cyclosporine (CsA) + antibody LO-Tact-1, 0.2 mg/kg/day from day +7 to day +28. Twelve additional patients were administered methotrexate (MTX) + CsA+antibody LO-Tact-1, 0.4 mg/kg/day from day -1 to day +28. The antibody was well tolerated. Engraftment was not affected. GVHD grade > or = II occurred in six of 15 and eight of 12 patients receiving CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (P = 0.52). GVHD grade > or = II developed in patients at a median of 32 and 34 days with CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (log-rank test, P = 0.57). GVHD contributed to death in four patients who were administered CsA+LO-Tact-1 and in one patient who was administered MTX+CsA+LO-Tact-1. Chronic GVHD occurred in two patients who were treated with CsA+LO-Tact-1 and in two patients treated with MTX+CsA+LO-Tact-1. Throughout therapy, serum levels of LO-Tact-1 ranged from 2 to 10 mg/l. There was no correlation between serum levels of LO-Tact-1 and the occurrence of GVHD. GVHD occurred in 10 patients during LO-Tact-1 prophylaxis. There was no significant difference between relapse or survival rates among the patient groups. We conclude that, while free of adverse effects, monoclonal anti-IL-2 receptor antibody LO-Tact-1 does not improve prophylaxis of GVHD in HLA-matched sibling BMT.