Photodynamic threshold doses in dogs with spontaneous tumors can be achieved through a mathematical model. For this to be clinically relevant, it is important to know the treatment parameters for tissue necrosis. The threshold dose for three photosensitizers (porfimer sodium, aluminum cholorophthalocyanine [AlClPc], and tin ethyl etiopurpurin [SnET2]) commonly used in veterinary chemotherapy protocols was evaluated in 12 dogs with spontaneous tumors. To derive the photodynamic threshold dose, the tissue optical properties of each compound were determined by diffuse reflectance and thus the light fluence rate. Uptake was measured by fluorimetry using tissue solubilization techniques. The threshold values calculated were highest for AlClPc (irradiated 48 hours after administration). The radius of necrosis (4.00 to 5.48 mm) and photosensitizer uptake (3.4 to 6.91 microg/g) were elevated after injection of porfimer sodium. The threshold dose model described here is photosensitizer dependent but independent of photosensitizer uptake and light dose. This study indicates that more photon absorption is needed for tumor necrosis with AlClPc than for either SnET2 or porfimer sodium.