Objective: Assess interaction of pazopanib, an oral antivascular endothelial growth factor inhibitor, with radiation in tumor xenograft models. Methods: Flank xenografts in female athymic nude mice of human lung cancer cell line, A549, and head and neck cancer cell line, UM-SCC-6, were allowed to grow to ∼5×5mm. Groups were then treated with pazopanib and/or escalating doses of radiation and tumor measurements over time compared with untreated tumor-bearing controls. Pazopanib (100mg/kg) began 7 days before radiation and continued for 28 days. Daily radiation was 0.5, 1, 2, or 3 Gy ×5 days. Results: Tumors in the A549 control group reached >4× the original size by day 36 postradiation. All treatment groups had less robust tumor growth (p<0.05) and the group receiving pazopanib+3 Gy radiation/day had tumor regression to less than baseline. In the UM-SCC-6-tumor-bearing animals, tumors in all treatment groups had less robust growth than untreated controls after day 23 post-treatment. Conclusion: The combination of pazopanib and radiation resulted in a trend of superior tumor growth inhibition compared with either agent alone. All treatment groups had impaired tumor progression compared with untreated controls. © Copyright 2014, Mary Ann Liebert, Inc. 2014.