We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1 and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37 patients with far advanced or non-curative resectable gastric cancer received NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80 mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy. The median number of courses administered was 3 (range 2-7), and 6 cases were treated on an outpatient basis only. The overall response rate was 62.2% (no CR, but 23 PR), and the individual response rates were 67.6% for the primary lesion, 90.5% for lymph node metastasis including para-aortic region, 50.0% for liver metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were generally mild, no treatment-related death and no serious adverse reactions were observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia, anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6 (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite loss and diarrhea of grade 3 were observed in only one (2.7%) patient at nonhematological toxicity. Twenty-four cases had undergone surgical treatment, and resection was performed in all cases. Seventeen of the 24 (70.8%) patients underwent curative resection. There was no major morbidity following surgery. The patients were favorable both for operation time (229 min) and bleeding volume (365 ml). The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage, ileus and 2 pancreatitis. Two-year survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients.