A light microscopic study was performed during the preictal period following the administration of methionine sulfoximine (MSO) to adult rats. The principal morphologic observation was the development of Alzheimer II astrocytes in gray matter, suggesting that the metabolic abnormality induced by MSO is initially confined to the astrocyte. In view of the association of the Alzheimer II astrocyte with hyperammonemic states, the drug toxicity may be secondary to the presence of ammonia. A possible mechanism involves astrocytes in the development of seizures produced by MSO.