A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.