Electrochemical measurements of transcutaneous tumor oxygen tension are combined with compartmentalized modeling techniques in order to develop a more complete picture of the early, oxygen-dependent events during photodynamic therapy (PDT). Irradiation of Photofrin II-treated VX-2 skin carcinomas in rabbit ears results in severe local oxygen depletion which is proportional to the applied light dose. For 50 mW/cm2 irradiations (at 630 nm), energy fluences of approximately 200- 300 kJ/m2 are required to irreversibly deplete tumor transcutaneous oxygen levels. Light-induced structural damage further decreases tumor oxygen tension by disrupting blood flow. Measured and modeled tumor oxygen depletion rates are used to estimate the production of cytotoxic oxygen intermediates as well as provide a qualitative assessment of tumor circulatory status.