Radioimmunotherapy (RIT) and radiotherapy (RT) were evaluated in nude mice developing liver metastases of human colon cancer. Without treatment, 90% of preconditioned nude mice, injected with LS174T cells intrasplenically and splenectomized, died between 26 and 93 days after grafting with few to several hundred liver metastases. RIT with 500 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies, injected i.v. in 3 weekly fractions, was initiated 1 to 3 weeks after grafting. Mean survival increase was 43 days for mice treated at 2 weeks. From 13 mice treated at 1 week, 8 mice showed long-term survival, a significantly better cure rate compared to RIT at 2 weeks. Mice undergoing RIT at 3 weeks showed similar survival as untreated controls. Mice injected with 131I-labeled irrelevant IgG1 or unlabeled antibody showed no significant survival increase. Conventional fractionated external beam RT of the liver showed that 40-50 Gy treatment initiated 1 week after grafting gave long-term survival in 7 of 13 mice, significantly better compared to RT at 2 weeks. With combined RIT + RT initiated 2 weeks after grafting, 5 of 11 mice had long-term survival in the absence of major toxicities. Thus, early RIT and RT were more efficient than later treatments, and combination therapy might give further improvement.