Sequential MTX/5-FU therapy was performed on 64 patients with unresectable or recurrent gastric cancer. The therapy was most effective in patients with poorly differentiated type gastric cancer. We adopted the intermediate (MTX: 100mg/m2, 5-FU: 800mg/m2) and low (MTX: 30mg/m2, 5-FU: 600 mg/m2) dose regimens. The latter was performed at the outpatient clinic every 2 weeks. This therapy was used for patients with Borrmann type 4 gastric cancer or advanced gastric cancer of poorly differentiated type as postoperative adjuvant chemotherapy. The response rate was 25% in 44 evaluable patients, and 33% in patients with poorly differentiated type cancer. As an adverse effect, leukopenia (grade 3, 4) was observed in 4 patients (9%). The 5-year cumulative survival rate of the sequential MTX/5-FU therapy group (52.6%) was much better than the conventional adjuvant chemotherapy group (32.1%) in patients who underwent curative resection with Borrmann type 4 gastric cancer. One patient survived more than 900 days after non-curative resection with peritoneal dissemination (P 3) after low dose therapy of sequential MTX/5-FU. For the patients who did not respond to the MTX/5-FU therapy, MTX/CDDP/LV/5-FU therapy was adopted. This protocol consisted of MTX (30 mg/m2 iv; day 1), CDDP (60 mg/m2 div; day 2 and day 9), Leucovorin (30 mg iv; day 2-9) and 5-FU (250 mg/m2 div; day 2-9). We also performed MTX/CDDP/LV/5-FU therapy for the treatment of differentiated type gastric cancer.