It has been shown that carbamazepine (CBZ) and valproic acid (VPA) have no significant negative or even positive side effects upon cognition in patients with epilepsy. The present study evaluated cognitive effects of CBZ or VPA in 16 patients with newly diagnosed epilepsy. Twelve patients had complex partial seizures, four patients primarily generalized seizures. Special attention was directed towards seizure type, presence of structural lesions and seizure control. Neuropsychological testing was carried out prior to medication and when drugs were within therapeutic ranges. Nineteen untreated healthy subjects served as controls. The following results were obtained: first of all, no general effect of antiepileptic drugs upon cognition could be detected. Only a subgroup with lesion (n = 8) and pre-existing cognitive deficits showed a significant decrease in memory performance during medication. This group additionally obtained poor seizure control. In conclusion, adverse cognitive changes under medication cannot be explained by antiepileptic drugs alone. The presence of cerebral lesions and obtained seizure control have to be considered as essential risk factors.