Focal ischemia was produced by occlusion of the right middle cerebral artery (MCA) in normo- and hyperglycemic rats. In the cortical infarct rim, regional [14C]2-deoxyglucose [( 14C]2-DG) phosphorylation was correlated to spontaneous transient changes in extracellular potassium recorded as direct current (DC) potential deflections. In normoglycemic rats the DC potential showed transient but recurrent deflections in the first hours following MCA occlusion. The 2-DG phosphorylation was elevated by 200% in the same area. In contrast, hyperglycemic rats had no, or a single, deflection of the DC potential in the rim, and the 2-DG phosphorylation remained normal. The same pattern was obtained by application of 3 M KCl to the exposed cortex. In normoglycemia potassium application resulted in recurrent deflections of the DC potential, and 2-DG phosphorylation increased in most parts of the hemisphere. Hyperglycemic animals had a nearly stable DC potential, and 2-DG phosphorylation increased only in the tissue area situated directly below the site of potassium application. The results indicate that metabolism in the cortical infarct rim is stimulated by spontaneous and recurrent changes in extracellular potassium--a phenomenon that may be related to spreading depression--and that the metabolism remained normal in the same area in hyperglycemic animals owing to an inhibition of transient increases of extracellular potassium.