Generalized corticoreticular epilepsy was established in adult cats by parenteral penicillin, and electroencephalographic monitoring was carried out. Ketamine HCI was injected intravenously in doses of 2.5 to 20 mg per kilogram. If doses of penicillin were inadequate to establish typical spike-wave activity, ketamine induced the spike-wave pattern typical of much higher doses of penicillin. At doses of penicillin that established the spike-wave pattern, ketamine potentiated the spike-wave activity and sometimes induced spike-and-wave status. These findings suggest caution in the clinical use of ketamine in patients with corticoreticular epilepsy. Because analogous effects have been observed upon administration of GABA-mimetic agents, GABA systems may play a role in ketamine anesthesia and corticoreticular epilepsy. Precollicular brain transections failed to modify ketamine effects, excluding a possible influence of mesencephalic centers on the observed potentiation.