There has long been an interest in the use of combination chemotherapy/radiotherapy in the treatment of gastrointestinal tumors. Almost all such regimens combined 5-fluorouracil (5-FU) with radiotherapy. Work has been done in gastric cancer, pancreatic cancer, and colon and rectal cancer, all of which demonstrate an advantage in certain clinical situations for combined-modality therapy. In locally advanced pancreatic cancer, radiotherapy/5-FU has been shown to improve survival compared with radiotherapy alone, while in resectable carcinoma of the pancreas, the combination has been demonstrated to improve long-term survival compared with surgery alone. In patients with gastric cancer the data are more limited, but indications are that combined-modality therapy may benefit certain subsets of patients. Little information exists in colon cancer, but patterns of failure suggest a potential role for adjuvant radiotherapy/5-FU. Studies are being designed to test the hypothesis. In rectal cancer, a significant amount of data exists to support the value of radiotherapy/5-FU-based chemotherapy as an adjuvant in patients with stages B2 and C tumors. At present, studies are being run or analyzed to define whether modulation of 5-FU with leucovorin or levamisole, or whether the use of continuous infusion 5-FU, will improve the therapeutic efficacy of the adjuvant therapy.