Evidence suggests that a specific subcortical pathway synaptically linking the anterior thalamic nuclear complex (AN) to the hypothalamus and midbrain is important in the expression of pentylenetetrazol (PTZ) seizures. Perturbation of neuronal activity along this path via focal disruption or chemical inhibition significantly raises seizure threshold. Recent data has demonstrated that focal electrical stimulation within the hypothalamic component of this pathway inhibited seizure expression in a current and frequency dependent fashion. Similar experiments were conducted in the AN to investigate the hypothesis that stimulation of this thalamic nuclear region can prevent the propagation of PTZ seizures between cortical and subcortical regions. Our results indicate that high frequency (100 Hz) stimulation of AN did not alter the expression of low dose PTZ induced cortical bursting but did raise the clonic seizure threshold compared to naive animals or those stimulated at sites near, but not in AN (P < 0.01). Low frequency stimulation (8 Hz) was in contrast, proconvulsant and could induce behavioral arrest responses accompanied by rhythmic high voltage EEG even without PTZ challenge. This data further highlights the role of AN in mediating the expression of seizures and provides experimental support for the concept that this thalamic region may be a promising target for focal stimulation to treat intractable seizures in humans.