The efficacy of high-dose post-operative radiation therapy was evaluated in 56 patients with pathologically proven or suspected residual disease after surgical resection of colon or rectal carcinoma. Patients had either microscopic or gross residual. They were treated with pelvic or abdominal irradiation to a dose of 4500 cGy followed by boost therapy to as much as 6000 to 7000 cGy if small bowel could be moved from the radiation field. Patients with microscopic residual had a local failure rate of 30% compared to 57% in those with gross residual disease. Five-year disease-free survival was 45% in patients with microscopic versus 10.6% for those with gross residual tumor. There was a trend toward a dose response curve for those with microscopic disease, but none was noted with gross residual. In view of the limited results obtained with current external beam techniques, it is recommended that newer avenues, such as high-dose preoperative therapy combined with intraoperative radiation, be investigated in this poor prognosis group.