Bioluminescent imaging (BLI) has found significant use in evaluating long-term cancer therapy in small animals. We have now tested the feasibility of using BLI to assess acute effects of the vascular disrupting agent Combretastatin A4 phosphate (CA4P) on luciferase expressing MDA-MB-231 human breast tumor cells growing as xenografts in mice. Following administration of luciferin substrate, there is a rapid increase in light emission reaching a maximum after about six minutes, which gradually decreases over the following 20 min. The kinetics of light emission are highly reproducible, however, following IP administration of CA4P (120 mg/kg), the detected light emission was decreased between 50 and 90 percent and time to maximum was significantly delayed. Twenty-four hours later, there was some recovery of light emission following further administration of luciferin substrate. Comparison with dynamic contrast-enhanced MRI based on the paramagnetic contrast agent Omniscan showed comparable changes in the tumors consistent with the previous literature. Histology also confirmed shutdown of tumor vascular perfusion. We believe this provides an important novel application for BLI, which could have widespread application in screening novel therapeutics expected to cause acute vascular changes in tumors.