The production of human monoclonal antibodies has been attempted using tetanus toxoid as a model antigen since a human antibody of this specificity could have clinical applications. Both mouse and human myeloma cell lines were used as fusion partners and the effects of in vivo and in vitro antigen boosting were also investigated. A cell line, ES12, which secreted specific tetanus toxoid antibody arose following fusion of lymphocytes from a donor who had been boosted three months earlier. Antibody was secreted by this cell line at a high titre (2.5 I.U/ml); it was of IgG isotype and it protected mice against challenge with tetanus toxin. This is, therefore, a first step in producing a therapeutically useful monoclonal antibody.