Dunn osteosarcoma cells injected i.v. into tumor-free isogeneic C3H/He mice resulted in artificial pulmonary metastases, which were treated by cyclophosphamide (100 mg/kg/day i.p. for 3 days) or single thoracic X-ray doses of 1500 rads either 1 or 14 days after tumor cell injection. Compared to untreated controls, reduction in lung colony number and increase in life-span for the 1-day metastases were 56 and 46% for radiated mice, and 100 and greater than 367% for cyclophosphamide-treated mice. Corresponding values for 14-day metastases were 42, 26, 85, and 98%, respectively. Nine of 44 mice bearing 1-day metastases treated by cyclophosphamide are surviving greater than 340 days after treatment. Both treatments resulted in the extension of life-span and reduction of the number of lung colonies, and, in both modalities, there was a reduced antitumor effectiveness when treatment was withheld until the disease was more advanced.