Basic haematologic parameters and serum gamma-glutamyl-transferase (GGT) activity were evaluated in a five-year prospective follow-up study of 25 patients with newly diagnosed epilepsy starting treatment with carbamazepine. In addition, we evaluated the effects of replacing carbamazepine by oxcarbazepine on these parameters, erythrocyte folate concentrations and serum vitamin B12 levels in 12 male patients with epilepsy. The mean white blood cell count (WBC) and red blood cell count decreased after 2 months carbamazepine therapy, and remained at this lower level during the first 5 years of medication. The mean erythrocyte volume (MCV) and the serum GGT activity increased progressively during carbamazepine treatment. The serum GGT activity decreased after replacing carbamazepine by oxcarbazepine indicating a normalization of the liver P450 enzyme system induction. Concomitantly, the erythrocyte folate concentrations and serum levels of vitamin B12 increased, and the WBC increased and MCV decreased. It is probable that the changes in folate metabolism and serum vitamin B12 concentrations are due to normalization of the liver P450 enzyme system induction after the change of medication. The haematologic changes during carbamazepine medication, and their normalization after replacing carbamazepine by oxcarbazepine are possibly related to changes in folate and vitamin B12 metabolism.