The epileptogenicity of caffeine and aminophylline was studied in rats. Intraperitoneal administration of caffeine produced an immediate excitation and seizures followed by an encephalopathy. A progression from encephalopathy to seizures was observed following aminophylline administration. During the development of behavioral seizures, the EEGs showed a progression from fast activity isolated or bursts of spikes and/or sharp waves to full-blown epileptiform discharges. A wide spectrum of cardiac arrhythmias was observed during and following the seizures. Epileptiform activities ranging from isolated or bursts of spikes and/or sharp waves to continuous epileptiform discharges were observed following local application of the drugs to the cerebral cortex.