Human lymphoblastoid interferon-alpha (IFN-alpha) has been coupled using N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to a murine monoclonal antibody (791T/36) which reacts with antigens expressed on human osteogenic sarcomas. The purified conjugates retain antibody activity as defined by their capacity to compete with binding of fluorescein isothiocyanate-labelled 791T/36 antibody to 791T cells. IFN-alpha-791T/36 antibody conjugates synthesized with 125I-trace-labelled IFN-alpha and 131I-trace-labelled antibody also bound to 791T cells, but not to bladder carcinoma T24 cells. The conjugates also retain the capacity of free IFN to activate natural killer cells in human peripheral blood lymphocytes and show specific localization in human osteogenic sarcoma xenografts developing in immunodeprived mice. These findings establish that conjugates containing IFN linked to a monoclonal antibody reacting with osteogenic sarcoma-associated antigens have potential for targeted immunotherapy and in related investigations with antibody has been shown by gamma camera imaging of patients following infusion of 131I-labelled antibody to localize in primary osteogenic sarcomas.