• Contralateral focal seizures occurred in rats following the intracortical injection of penicillin into the anterior motor cortex. The anatomic dimensions of the metabolic response in the focus as well as the spread of increased activity through the brain were studied by autoradiography following intravenous injection of carbon 14-labeled 2-deoxyglucose. Injections of 25 to 200 units of penicillin resulted in mild to severe contralateral motor jerks coincident with repetitive single spike discharges on the electroencephalogram. Concurrent autoradiography revealed a 1.3- to 2.5-fold increase in metabolic activity in discrete areas in ipsilateral cortex, basal ganglia, thalamus, and contralateral cerebellum. Intracortical injections of over 300 units resulted in the development of recurrent contralateral tonic-clonic seizures, with 20% becoming bilateral. In brains of these animals there was activation of bilateral medial frontal cortex, bilateral extrapyramidal system, thalamus, cerebellum, and limbic structures.