Three patients with anacidotic hyperglycemia and focal seizures died despite appropriate therapy; autopsy in two disclosed cerebral infarcts. In the literature, 20 patients with anacidotic hyperglycemia (approximately 14%) had seizures and of these, 17 had focal seizures. Although the various biochemical abnormalities that appear in this syndrome are known to evoke seizures singly or in combination, the pathogenesis of the focal epilepsy in this disorder is ill understood. A review of the previously reported occurrences indicates that the total metabolic derangement, rather than an isolated biochemical abnormality, occurring in patients with cerebrovascular insufficiency is the most likely explanation. We suggest also that anacidosis, by interfering with the formation of γ-aminobutyric acid, a neuronal inhibitor, may play an important role in the production of seizures.