Although functional imaging with positron emission tomography (PET) and single-photon emission computed tomography are useful in the clinical evaluation of intractable epilepsy, these techniques have not been widely applied to understanding the basic mechanisms of the epilepsies. Among patients with infantile spasms, PET studies with 2-deoxy-2[18F]fluoro-D-glucose (FDG) suggest that the spasms are the result of secondary generalization from cortical foci and that maturational factors result in the recruitment of basal ganglia and brainstem serotonin mechanisms that lead to secondary generalization and the unique semiology of the spasms. Attempts to develop an animal model of infantile spasms have not been successful. Glucose utilization studies in the Lennox-Gastaut syndrome also indicate cortical lesions and further suggest that the electroencephalographic pattern of 1 to 2.5 Hz spike-wave activity (slow spike-wave pattern) is an interictal phenomenon. There is a remarkable consistency between 14C-2-deoxyglucose autoradiographic findings and PET observations of glucose utilization performed for patients in the ictal, interictal, and postictal states. Although three patterns of ictal glucose hypermetabolism have been described, hypermetabolism also can be seen in the postictal and interictal clinical states and in various animal models. Preliminary studies of benzodiazepine receptor binding with PET have found that the cortical epileptic region of decreased binding is smaller than the region of hypometabolism on glucose utilization studies, but detailed electrophysiologic comparisons have not been made. Development of new PET methods for the study of presynaptic and postsynaptic neurotransmitter functions will offer unique opportunities in the study of epileptic mechanisms.