Vascular endothelial growth factor (VEGF) is one of the most potent mediators of both physiologic and pathologic angiogenesis. Normal physiologic induction of VEGF occurs during periods of extreme growth, wound healing, as well as immune inflammatory response. Pathologically, however, VEGF is largely responsible for tumor induced angiogenesis and cell survival. Traditional methods of VEGF expression analysis involve either in vitro studies, or highly invasive in vivo methods. We have developed a unique transgenic mouse model (VGL) that possesses a truncated human VEGF promoter attached to a GFP-Luciferase fusion protein. Incorporating this model with both spontaneous and orthotopically injected tumors allow VEGF promoter activity to be visualized in vivo by luciferase luminescence in response to tumor growth non-invasively and over time. By also utilizing bioluminescent tumor cells, we were able to generate models that identify host, tumor, or combined VEGF promoter activity. Results indicate that tumor tissue is responsible for the majority of VEGF promoter activity during tumor growth. Additional studies into the mechanism by which tumor cells initiate VEGF production will yield much needed insight into tumor survival. In conclusion, we have shown that the VGL bioluminescent mouse model is indeed capable of yielding compelling information on host-tumor interactions.