Interferon-alpha (IFN-Alpha) + cisplatin (CDDP) + 5-FU therapy was given to 10 patients with gemcitabine (GEM)-refractory unresectable or recurrent pancreatic cancer. CDDP (35 mg/m(2)) was administered intravenously on the first day, IFN-Alpha (5x10(6)IU) subcutaneously on day 2,4 and 6 of each week, and 5-FU (175 mg/m(2)/day) continuously infused every day for 4 weeks. The 10 patients consisted of 8 men and 2 women with a mean age of 56.2 years. As the main site of progression, 5 patients had liver metastases, 1 had lung metastases, 2 had peritoneal dissemination, and 2 had local recurrence. The objective response rate was 30%, including 1 complete response. Grade 3 anorexia, neutropenia and thrombocytopenia occurred in 60%, 40% and 40%, respectively. IFN-Alpha + CDDP + 5-FU therapy is an effective treatment for GEM-refractory pancreatic cancer, but with moderate toxicity.