In this report a new approach for the identification of pathological changes in scrapie-infected Syrian hamster brains using Fourier transform infrared microspectroscopy is discussed. Using computer-based pattern recognition techniques and imaging, infrared maps with high structural contrast were obtained. This strategy permitted comparison of spectroscopic data from identical anatomical structures in scrapie-infected and control brains. Consistent alterations in membrane state-of-order, protein composition, carbohydrate and nucleic acid constituents were detected in scrapie-infected tissues. Cluster analysis performed on spectra of homogenized medulla oblongata and pons samples also reliably separated uninfected from infected specimens. This method provides a useful tool not only for the exploration of the disease process but also for the development of rapid diagnostic and screening techniques of transmissible spongiform encephalopathies.