Thirty evaluated patients were randomized to either continuous radiation + 5-FU (16 patients), or split-course radiation + 5-FU (14 patients) for the treatment of residual, recurrent, or inoperable carcinoma of the rectum or recto-sigmoid. Twenty-one of these patients received maintenance MeCCNU + 5-FU chemotherapy following radiation. Entry was terminated when late treatment reactions were seen in the precursor pilot study. Twenty-four of the patients have died; the estimated median survival is 17 months in each of the treatment arms. Performance status was the only significant prognostic factor for survival. The rate of severe, acute reactions during the radiation treatment period was higher for the continuous-course than for the split-course regimen (69 vs. 21%, p = .01). The rates of severe late treatment reactions, 23% (7 of 30), and severe chemotherapy toxicity, 48%, were similar for the two treatment programs. Late treatment reactions, primarily bowel complications, were seen from 3 to 23 months after radiation in 3 patients treated with continuous course, and 4 patients treated with split course. Ten of 21 patients (48%) who received maintenance chemotherapy had severe or worse toxicity. Toxicity was seen for 6 of 12 continuous-course, and 4 of 9 split-course patients. Twenty-seven patients have had disease progression, and the median length of disease control is 11 months.