PTK787/ZK 222584 is an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. In this study, the effectiveness of PTK787/ZK 222584 and radiation on canine oral melanoma xenografts was assessed. Xenografts were treated with radiotherapy (4 · 6 Gy), or with PTK787/ZK 222584, or with a combination of both. Treatment efficacy was assessed using a tumour growth delay assay, serial power Doppler and pO2 measurements during and after therapy. There was a significant growth delay for the group treated with radiation alone and for the combined treatment group. However, tumour growth delay was similar in both groups. Tumours were hypoxic before irradiation and no significant re-oxygenation occurred during therapy. In all tumours, vascularity and perfusion were significantly lower at the end of the study but no significant differences in perfusion, vascularity and oxygenation status were observed between and within treatment groups. The combination of PTK787/ZK 222584 and radiotherapy did not perform better than radiotherapy alone in this model.