The treatment of patients with osteosarcoma continues to result in few survivors despite advances in surgery and radiotherapy. Since the primary site of failure is pulmonary, it is apparent that a systemically active adjuvant must be employed if a cure is to be achieved. Because of the experimental evidence for an immune response against osteosarcoma and because of the potential systemic activity of the immune system, a trial of postoperative adjuvant immunotherapy was begun. Seventeen patients received immunotherapy consisting of BCG and an allogeneic tumor cell vaccine following surgical removal of all gross tumors. Eighteen per cent (3/17) of the patients who received immunotherapy remained alive and free of disease compared to 0/12 who did not. An analysis of the 14 patients with recurrence, revealed that the median time to recurrence was 3.0 months in both groups. It is, therefore, apparent that at the time of initiation of immunotherapy subclinical metastasis must already have been present. Therefore, on the basis of this study we conclude that adjuvant chemotherapy should be employed to further reduce the tumor cell burden in order for immunotherapy to be effective for osteosarcoma.