Our aim was to determine the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and recommended dose of oxaliplatin combined with oral tegafur-uracil and leucovorin. Twenty-eight chemo-naive patients with advanced gastric cancer were enrolled. Oxaliplatin (55, 70, 85, 100 and 115 mg/m2) was given as a 2-h infusion on days 1 and 15. Oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) were given 3 times a day from days 1 to 21 (28-day cycle). DLTs were defined as grade IV hematologic toxicity or grade III non-hematologic toxicity. The MTD for oxaliplatin was 100 mg/m2. The most common DLT was diarrhea. Major grade III/IV toxicities included vomiting, diarrhea, renal dysfunction, leukopenia and thrombocytopenia. There were two treatment-related deaths. Intent-to-treat response was graded as partial response in 13 patients (46.4%; 95% confidence interval 26.74-66.12%), stable disease in nine and disease progression in five. As of June 2004, 17 patients had died. The median time to treatment failure, time to progression and overall survival were 124, 308 and 434 days, respectively. The recommended dose for the phase II study is oxaliplatin 100 mg/m2 biweekly with oral tegafur-uracil (300 mg/m2 per day) and leucovorin (60 mg/day) 3 times a day for 21 days.