The observation of photobleaching is affected by the tissue optics. The apparent time constant for photobleaching at a particular irradiance of light is related to the true photobleaching constant, D, in J/cm2 by a factor which depends on the tissue optical properties, especially at the wavelength used to excite fluorescence. We report in vivo experimental measurements of protoporphyrin IX (PPIX) photobleaching in subcutaneous rat tumors which suggest tentative values for D of about 105 ± 23 J/cm2 during 630 nm irradiation. The effect of such a photobleaching constant on the photodynamic dose, P, in photons/cm3 absorbed by PPIX, was calculated. We estimate that an initial PPIX concentration of about 0.2 μg/ml is required such that P reaches twice the toxic threshold photodynamic dose, Pth, which is assumed to be similar to the 8.6 × 1017 value cited for PhotofrinII. The above estimates are subject to further investigation. This paper presents the mathematics underlying the process of photobleaching and its observation based on fluorescence monitoring.