Fifteen patients, median age 64 years, presenting with advanced gastrointestinal adenocarcinomas, were included in this study. The treatment combination consisted of folinic acid (200 mg/m2, IV bolus injection) followed by 5-fluorouracil (5-FU; 400 mg/m2, 30-min infusion) for 5 consecutive days and mitomycin C (10 mg/m2, IV bolus injection) on day 1, the therapy being resumed every 21 days. An objective response was noted in 7 of 15 patients (47%): 1 complete and 6 partial responses, including 4 of 5 patients who had received no prior chemotherapy and 3 of 10 patients who previously failed to respond to 5-FU. Objective responses were encountered in 4 of 7 stomach cancers, 2 of 3 pancreas tumors, and in only 1 of 5 colorectal carcinomas. Furthermore, 9 of 11 patients were completely relieved of their abdominal pain. The median duration of remission was 5 months. The median survival time of patients who responded to treatment was 7 months. Toxicity was acceptable, with mainly leukopenia and/or thrombocytopenia (5 patients) and oral mucositis (3 patients), leading to dose reduction. The combination of 5-FU+ folinic acid + mitomycin C appears to be a potentially effective regimen in the treatment of advanced gastrointestinal tumors, even in patients previously treated with 5-FU.