Systemic chemotherapy for advanced gastric cancer is frequently associated with significant treatment-related toxicity, which is particularly serve in patients presenting with a poor general condition. A search for effective and low-toxic regimens for this group of patients is mandatory. A weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (HDFL) has previously been demonstrated to be an effective treatment for advanced colorectal cancer with minimal toxicity. In the past 3 years, this regimen has been tested at our institutes in patients with advanced gastric cancer, the general condition of whom had made the use of intensive combination chemotherapy impossible. The regimen consisted of a weekly 24-hour infusion of 2,600 mg/m2 of 5-FU and 300 mg/m2 of leucovorin. From August 1992 to December 1995, 34 patients had been treated with this regimen for a total of 488 courses (average: 14.4 per patient). Hematological toxicity of this regimen was minimal, with grade 3 or 4 leukopenia developing in only 1 (2.9%) patient. Other nonhematological toxicities were also negligible except a reversible neurotoxicity which developed in 2 patients. Twenty-five patients were eligible for response analysis. One complete response, 11 partial responses, 5 stable diseases, and 8 progressive diseases were observed. The response rate was 48% (32-72%, 95% CI). The median overall survival (OS) of the whole group was 7 months (range: 1-18+). The median OS and time to progression of the responders were 8.5 months (range: 2-18) and 5 months (range: 2-10+), respectively. The palliative effect was satisfactory with the Karnofsky performance status of the responders improving from a median of 50% (range: 20-90%) to 70% (range: 50-100%). Our retrospective data suggested that HDFL is an effective and low-toxic palliative treatment even in patients with a very poor general condition. We advocated that this regimen should be further tested in ordinary patients with advanced gastric cancer.