The chorioallantoic membrane (CAM) assay is a widely used bioassay in early in vivo cancer research. The CAM allows non-invasive study of in vivo microvasculature and blood circulation. This report describes the first topical application investigation of photodynamic response in the CAM model using Hypericin (HY) and Hypocrellin B (HB) that belongs to the perylenequinone family. Briefly, cultivated carcinoma of the human bladder cell line (MGH), were inoculated on the CAM of fertilized eggs of embryo age (EA) 9. Tumor growth was evaluated by digital stereomicroscopy. Photodynamic therapy (PDT) was performed following topical application of the photosensitizers. We were able to demonstrate that these perylenequinones localized selectively in the xenografted bladder tumor and in the vasculature of the CAM. Photodynamic treatments were performed using a custom-made non-laser light source coupled into a flexible fiber bundle to selectively excite the photosensitizers in order to induce photodamage to the tumor and vasculature. The vascular damage induced was quantitatively measured following topical application of the photosensitizers. Both photosensitizers exhibited very similar degrees of photodamage to the CAM. The CAM model offers an exciting avenue for the study of PDT induced effect on the vasculature. Our preliminary results support that the CAM model could potentially serve as a customized model to study photodynamic therapy effects of various photosensitizers on specific tumor models.