Forty-five outpatients with chronic epilepsy with complex partial seizures (CPS) alone or associated with secondarily generalized tonic-clonic seizures (SGTCS) were treated with carbamazepine (CBZ) monotherapy. All patients had only a unilateral scalp electroencephalographic (EEG) focus. Left- (n = 29) and right- (n = 16) sided foci patients were comparable for age, sex, duration, and etiology of epilepsy as well as total and free CBZ serum levels. CBZ significantly improved CPS irrespective of the side of the EEG focus, whereas SGTCS were controlled for greater than 1 year in 15 of 19 patients with left focus and in three of 11 patients with right focus. When patients with poorly controlled seizures discontinued CBZ and changed to other therapies, they achieved a significant reduction in number of SGTCS, whereas the number of CPS was unchanged. The side of EEG focus seemed to be relevant to the control of SGTCS by CBZ. Interhemispheric neurotransmitter asymmetries may be involved in the EEG focus side-dependent CBZ response.