In a previous study we demonstrated that increased FOS expression in the amygdala induced by partial kindling seizures could be attenuated by administering c-Fos specific antisense oligonucleotides. In addition, we found that the administration of c-Fos antisense oligonucleotides at the beginning of the amygdala kindling process facilitated the appearance of stage V kindled seizures. In the present study, we evaluated the effect of the suppression of FOS on the expression and severity of the generalized fully kindled seizures as well as on the susceptibility to additional ictal events during the postictal and interictal periods. We observed that the administration of c-Fos antisense oligonucleotides did not modify the behavioral and electrographic manifestations of generalized stage V kindled seizures. However, c-Fos antisense oligonucleotides significantly reduced the susceptibility to additional ictal events during the postictal refractory period. Hence, the increased FOS protein induced by generalized tonic clonic seizures may participate in postictal mechanisms.