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A general model of tissue fluorescence which can be used to both (1) determine chemical and physical properties of the tissue and (2) design an optimal algorithm for clinical diagnosis of tissue composition is described. The model is based on a picture of tissue as a single, optically thick layer, in which fluorophores and absorbing species are homogeneously distributed. As a specific example, the model is applied to the laser-induced fluorescence of normal and atherosclerotic human aorta using 476-nm excitation. Methods for determining the relevant attenuation and fluorescence lineshapes are detailed, and these lineshapes are used to apply the model to data from 148 samples. The model parameters are related to the concentrations of the major arterial chromosphores, structural proteins, hemoglobin and ceroid. In addition, the model parameters are used to derive diagnostic algorithms for the presence of atherosclerosis. Utilizing a binary classification scheme, the presence or absence of pathology was determined correctly in 88% of the cases.