From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri-operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients.