The present invention is drawn to methods and compounds for transcutaneous photodynamic therapy (“PDT”) of a target tissue or compositions in a mammalian subject, which includes administering to the subject a therapeutically effective amount of a photosensitizing agent or a photosensitizing agent delivery system or prodrug, where the photosensitizing agent or photosensitizing agent delivery system or prodrug selectively binds to the target tissue; and irradiating at least a portion of the subject with light at a wavelength absorbed by the photosensitizing agent or if prodrug, by a prodrug product thereof, where the light is provided by a light source, and where the irradiation is at low fluence rate that results in the activation of the photosensitizing agent or prodrug product. These methods of transcutaneous PDT are useful in the treatment of specifically selected target tissues, such as: vascular endothelial tissue; abnormal vascular wall of tumors; tumors of the head and neck; tumors of the gastrointestinal tract; tumors of the liver; tumors of the esophopharyngeal; tumors of the lung; lymphoid tissue; lesions in the vascular system; bone marrow and tissue related to autoimmune disease.