Infrared (IR) microspectroscopy was used to detect disease-associated molecular changes spatially resolved in cryosections of scrapie-infected tissue of the CNS. The results show that IR spectra can be used for the discrimination between normal and 263K scrapie-infected hamster nervous tissue not only in the terminal stage of the disease but also in early clinical and even in the preclinical stage at 90 d after oral infection. The nuclei of the cranial nerves located in the medulla oblongata were especially well suited for an early detection of the diseased state by IR microspectroscopy. The most prominent molecular changes indicated by the IR spectra were located between 1300 and 1000 cm(-1), a region that contains contributions primarily from carbohydrates and the phosphate backbones of nucleic acids but also from membrane constituents.