Background: There are few therapeutic options in patients with colorectal cancer that progressed or recurred after initial 5-fluorouracil (5-FU) therapy. Many different 5-FU-based regimens and biochemical modulations that can potentiate the cytotoxic effects of 5-FU have been investigated in these patients. We evaluated the efficacy and toxicity of combination of 5-FU, leucovorin, levamisole and cisplatin (FLLP) salvage combination chemotherapy in progressive or recurrent colorectal cancer after 5-FU/leucovorin chemotherapy. Methods: Twenty-eight patients were enrolled in this study from April 1995 to July 1999. Patients received cisplatin (60 mg/㎡) administered on day 1, followed by leucovorin (20 mg/㎡) and 5-FU (375 mg/㎡) by rapid intravenous push for 5 consecutive days on day 1∼5. Levamisole was given or ally at a dose 50 mg three times a day on day 1∼3 & day 15∼17. Treatment courses were repeated in 4-week intervals. Results: Twenty-two patients were evaluable after treatment . Objective tumor response was in 4 of 22 (18.2%). The complete response, partial response, stable disease were 4.5% (1/22), 13.7% (3/22), 31.8% (7/22) respectively. The median response duration was 5.5 months. The median time to progression was 5.8 months. The overall median survival duration was 8.7 months and response group lived significantly longer than non-response group (not yet reached vs. 7.9 month, p=0.03). WHO grade 3-4 leukopenia occurred in 14%, nausea and vomiting 9%, but there was no treatment related death. Conclusion: We concluded that evaluation of this regimen appears relatively safe, with modest response as a salvage chemotherapy in patients who were previously exposed to 5-FU containing regimen. (Korean J Med 61:424-429, 2001)