The monoamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability. In the present work, we have described the effects of serotonin (5-HT) depletion after the administration of 5,7-dihydroxytryptamine (5,7-DHT) into the median raphe nucleus in rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus as well as the spontaneous seizure frequency during the chronic period of the model was determined. Since the hippocampus is one of the main structures in the development of this epilepsy model, the 5-HT levels in this region were also determined after drug administration. Sixty-three percent of 5,7-DHT pre-treated rats (15/24) and only 33.4% of those receiving the control solution (9/24) progressed to motor limbic seizures evolving to status epilepticus, following the administration of pilocarpine. The frequency of seizures during the chronic period, in epileptic rats that received 5,7-DHT, showed a significant (58%) increase after the treatment, when compared with control group. Our data showed that serotonin may play an important role on seizure activity which seems to be exerted by its inhibitory action on the expression of overt behavior seizures departing from an established focus in the limbic system.