Seventy-five patients with gastrointestinal cancer were entered in this study. The number of eligible cases were 38 in the group treated with sequential methotrexate (MTX)/5-fluorouracil (5-FU) with 5'-deoxy-5-fluorouridine (5'-DFUR) (group A) and 34 in the group without 5'-DFUR (group B). The treatment schedules were as follows: MTX/100 mg/m2 was given intravenously (i.v.) followed by 5-FU 600 mg/m2 i.v. 2 hours later and leucovorin 15 mg/body i.v. 8 and 20 hours later. This cycle was repeated once a week. In group A, 5'-DFUR 1,200 mg/body/day was given orally 5 consecutive days per week. Three of 35 cases in group A showed PR, while no case showed PR in group B. Median survival time was 5.0 months in group A and 5.3 months in group B, respectively. Gastrointestinal toxicity was commonly observed, and diarrhea was more frequent in group A (p < 0.05).