The majority of children who have febrile seizures will require no treatment other than parental reassurance. But, in some situations, the parents' anxiety level remains very high even after reassurance, and long-term management of febrile seizures may focus on decreasing parental anxiety. In these severe cases, phenobarbital is the most widely prescribed anticonvulsant drug. Its long-term use may have adverse effects on the various organ systems. Among them, the toxic effect on DNA presents one of the most important medical problems. The aim of the study was to determine the potential mutagenic effects of long term monotherapy with phenobarbital by means of comet assay in the peripheral blood lymphocytes of children with simple febrile seizures. Twenty-seven children with simple febrile seizures between the ages 29-54 months receiving long-term phenobarbital monotherapy for 7 to 27 months were studied. Control group consisted of 20 healthy sister or brothers of the patients who didn't use any long-term drug. No statistical difference between patient and control groups on comet scores were found (p>0,05). Some physician may believe that prevention of future febrile seizure is indicated because of the high degree of parental anxiety. In such a situations, we suggest that it is not necessary to consider the potential mutagenic effects of long-term phenobarbital monotherapy.