Dendritic cells (DCs) are potent antigen-presenting cells capable of inducing primary T-cell responses. Several immunotherapy treatment strategies involve manipulation of DCs, both in vivo and ex vivo, to promote the immunogenic presentation of tumor-associated antigens. In this study, an electrofusion protocol was developed to induce fusion between osteosarcoma cells and allogeneic bone marrow-derived DCs. Preimmunization with irradiated electrofusion products was found to provide partial or complete protection from tumor challenge in the UMR106 tumor model. Vaccinated survivors developed long immunological memory. The therapeutic potential of this type of approach was suggested by the ability of UMR106-DC electrofusion products which could induce tumor rejection in a substantial percentage (60%) of hosts bearing pre-established tumor cells. These results tended to indicate that treatment with electrofused tumor cells and allogeneic DCs might be capable of inducing a potent antitumor response and could conceivably be applied to a wide range of cancer indications for which tumor-associated antigens have not been identified.