A method is demonstrated for the noninvasive detection and study of spreading cortical depression. Spreading depression (SD) was elicited in rats by topical application of potassium chloride to the exposed cortex. The apparent diffusion coefficient (Dapp) of water in a region of the cortex, measured using a PFG-NMR spin echo sequence with an observation time of 40 ms, declines 35% within 30 s and recovers to the normal value within the next 30 s. The region of decreased Dapp was shown to be 2 mm in size and to move in the cortex, away from the point of application, with a uniform velocity of 3.3 +/- 0.5 mm/min. The behavior of the affected region is consistent with other reports of the behavior of SD as monitored by electrophysiological means. The technique can be implemented on currently available MRI equipment and makes possible the noninvasive study of SD in animal models of neurological disorders, their therapeutic intervention, and possibly the study of SD in humans.