Nonconvulsive seizures from prefrontal cortex in humans cause complex behavioral, motor, and autonomic manifestations. In order to gain insight into the possible anatomical basis of these phenomena, we have studied experimental seizures from medial and lateral prefrontal-limbic cortex and the amygdaloid complex in rat. Small injections of penicillin or electrical stimulation were used to induce seizures, and the [14C]deoxyglucose technique was employed to map pathways of seizure spread. Analysis of results indicates that prefrontal-limbic cortex and amygdala exhibit strong bilateral reciprocal interaction. Mild seizures from these different areas activated both unique and similar pathways and targets. With increasing strength of discharge from these areas, there was a convergence of the subcortical pattern of activation in medial and midline thalamic nuclei and bilateral substantia nigra. These studies suggest that complex epileptic phenomena in humans evoked from a prefrontal seizure focus relate to activation of cortical and subcortical functional limbic anatomy.