We report an investigation of the therapeutic efficacy and safety of TS-1 single-agent therapy administered as first-line therapy in 23 cases of unresectable advanced gastric cancer treated at our institution. TS-1 was administered at 80 mg-120 mg (divided into two doses) per day for 28 days followed by a 14-day rest interval, making up a single cycle. The response rate for its antitumor efficacy was 39.1%, with partial response in nine cases, no change in seven cases, progressive disease in five cases, and two cases not evaluable (9 5% confidence interval: 19.7%-61.5%). By site, the response rate was 43.5% for primary tumors (10/23), 33.3% for lymph nodes (3/9), and 16.7% for liver metastasis (1/6). In 1 patient, the carcinomatous ascites disappeared,and in 3 patients they decreased remarkably. No significant differences were observed with regard to age (70 and over/under 70) or histological type (differentiated/undifferentiated). The one-year survival rate was 32.8%, and the 50% survival period was 29 9 days. The most common side effect was leucopenia in seven cases (30.4%), followed by decreased hemoglobin, loss of appetite, hepatic dysfunction and the like. Most side effects, however, were mild and did not exceed grade 2; grade 3 side effects were seen only in two cases (8.7%) of leucopenia and two (8.7%) of hepatic dysfunction, a low rate of occurrence. The outpatient follow-up ratio(outpatient period/total treatment period) was high at 69.6%, meaning that first-line single-agent therapy with TS-1 is beneficial in terms not only of efficacy but also in maintaining quality of life.