The antibodies and their protective activity in response to tetanus toxoid in man were studied by producing human antitetanus monoclonal antibodies after transformation of peripheral blood lymphocytes with Epstein Barr virus. Two human monoclonal IgG that reacted with the heavy chain of the toxin were obtained. One of them binds the COOH-terminal moiety and the other the NH2-terminal moiety. Only the NH2-terminal specific monoclonal antibody neutralized toxin in mouse, but in doses approximately 100-fold higher than those of a polyclonal antiserum. However, the association of these 2 antibodies was protective with doses lower than necessary for the monoclonal antibodies alone. To replace the polyclonal antibodies used, a good protection could be achieved by mixed human monoclonal antibodies against different epitopes of tetanus toxin.