Background: Radiotherapy is an established treatment for malignant localised disease. Pancreatic cancer however seems relatively insensitive to this form of therapy. Methods: Pancreatic cancer cell lines MiaPaca-2 and Panc-1 were pre-treated with 3000 IU/ml IFN alpha or 100 IU/ml IFN beta followed by 0, 2, 4, or 6 Gray (Gy) irradiation. Colony forming assay was used to assess the effects on cellgrowth. To measure the surviving fraction at the clinically relevant dose of 2 Gy (SF2), cells were pre-treated with 1000-10.000 IU/ml IFN alpha or 50-500 IU/ml IFN beta followed by 2 Gy irradiation. Results: The plating efficiency was 49% for MiaPaca-2 and 22% for Panc-1. MiaPaca-2 was more radiosensitive than Panc-1 (surviving fraction of 0.28 versus 0.50 at 4 Gray). The SF2 of MiaPaca-2 was 0.77 while the SF2 of Panc-1 was 0.70. The SF2 significantly decreased after pretreatment with IFN alpha 1000 IU/ml (p < 0.001) and IFN beta 100 IU/ml (p < 0.001) in MiaPaca-2 and with IFN alpha 5000 IU/ml (p < 0.001) and IFN beta 100 IU/ml (p < 0.01) in Panc-1. The sensitising enhancement ratio (SER) for IFN alpha 3000 IU/ml was 2.15 in MiaPaca-2 and 1.90 in Panc-1. For IFN beta 100 IU/ml the SER was 1.72 for in MiaPaca-2 and 1.51 in Panc-1. Conclusions: Type I interferons have radiosensitising effects in pancreatic cancer cell lines. This radiosensitising property might lead to an improved response to treatment in pancreatic cancer. Interferon beta is the most promising drug due to its effect in clinically obtainable doses. (C) 2011 Elsevier Ltd. All rights reserved.