This study was conducted to establish the optimum postoperative adjuvant chemotherapy with 5-FU in patients with gastric cancer. Seventy gastric cancer patients were treated after surgery with one of the following regimens; 5-FU 10 mg/kg/24 hrs c.i.v. x 24 days (arm A, n = 25); 5-FU 20 mg/kg/24 hrs c.i.v. x 4 days/w x 3 courses (arm B, n = 16); 5-FU 30 mg/kg/24 hrs c.i.v. x 2 days/w x 4 courses (arm C, n = 25). Blood 5-FU concentration, adverse effects and prognosis in each arm were compared. Changes in blood 5-FU concentrations were dose-related. The three-year survival rates in arms A, B and C were 15.0, 13.5 and 0.0%, respectively; they tended to be greater in arms A and B, but differences were not statistically significant. The most frequent adverse effects of the treatments were gastrointestinal, such as stomatitis. The incidence of reactions tended to be low in arm C, i.e., high-dose intermittent administration. Arm B (4 days-on, 3 days-off) was modified to 4 days-on, 6 days-off (arm B'), because severe stomatitis developed. The severity and incidence of stomatitis were reduced in the modified arm B group. We believe that intensive postoperative adjuvant chemotherapy for patients with gastric cancer should be designed using the arm B' approach.