We report our series of drug resistant epileptic patients submitted to callosotomy. The 25 patients were affected by severe epilepsy with invalidating generalized seizures with fall, lacking of indication for ablative surgery. Nineteen patients, with at least 1 year of follow-up, were considered for this study. The surgical outcome was classified as: class A), seizure disappearance; class B) 80%, class C) 80-50%, class D) less than 50% seizure reduction; E) increase of seizure frequency. The follow-up analysis shows that the better results are obtained with the generalized seizures, in particular the GTA. Our surgical results are discussed considering the data of the literature: about the functional anatomy of the Corpus Callosum, the experimental studies and the clinical series published on callosotomized epileptic patients.