Monotherapy is preferable in the treatment of epilepsy; a new antiepileptic drug has to be checked on its efficacy in monotherapy. In this study patients who had successfully been treated with loreclezole in previous studies were gradually withdrawn from their antiepileptic comedication. Nine patients participated in the study. Reduction of comedication was well tolerated in all, no serious side effects occurred. In 6 patients seizure frequency remained unchanged, i.e., within 50% limits. Two patients experienced a clear increase in seizure frequency. In 2 patients reintroduction of a second antiepileptic drug was mandatory. One patient experienced a further reduction in seizure frequency when monotherapy was reached. This observation indicates efficacy of loreclezole, also in monotherapy.