This study compares the photosensitizer concentration measured non-invasively in vivo by diffuse reflectance spectroscopy with the results of post mortem tissue solubilization and fluorometric assay. The reflectance spectrometer consists of a fiber optic surface probe, spectrometer, and CCD array detector. The surface probe has eight fibers separated from the light source fiber by distances ranging from .85-10 mm. The imaging spectrometer disperses the light from each detector fiber onto the 2D CCD array, while maintaining spatial separation of each individual spectrum. A single exposure of the CCD therefore captures the reflectance spectrum at eight distances and over a range of 300 nm. From the spectra, the tissue's optical scattering and absorption properties are determined using a diffusion model of light propagation. Changes in the tissue absorption are used to estimate the photosensitizer concentration. Normal NZW rabbits were injected with AlPcS4 and probe measurements made 24 hours after injection on the dorsal skin, on muscle after surgically turning the skin back, and on liver. A comparison of the noninvasive concentration estimates to the post mortem assay results finds good agreement for liver tissue. For skin, the non- invasive estimate is proportional to the true concentration, but low by a factor of 3. Based on Monte Carlo modeling of multilayered systems, this underestimate is attributed to the layered structure of the skin and nonuniform AlPcS4 distribution.