The purpose of the present study was to compare the pharmacokinetic parameters of two carbamazepine (CBZ) tablet formulations (conventional (CBZ-CO) and controlled-release (CBZ-CR)) in patients with epilepsy receiving the drug as monotherapy or polytherapy. The absorption rate constant (Ka), steady-state volume of distribution (Vdss) and total clearance (CL) were computed with the APIS software using 31 blood level profiles from 23 patients who were divided into four groups: patients receiving CBZ-CO in polytherapy, the same patients switched to CBZ-CR in the same polytherapy conditions, patients receiving CBZ-CO in monotherapy and patients receiving CBZ-CR in monotherapy. The four groups were compared in order to assess the significance of differences in Ka, Vdss, CL and diurnal fluctuations of plasma CBZ concentration. The results show a significant decrease of the Ka in the CBZ-CR groups compared to the CBZ-CO groups, both on monotherapy and on polytherapy. The comparison between the monotherapy and polytherapy groups shows increases of Vdss and CL, both in CBZ-CO and CBZ-CR polytherapy groups. Dispersion of pharmacokinetic data was higher in patients on CBZ-CO; among patients on CBZ-CR, dispersion was lowest in the monotherapy group. Clinical improvement was found in four of eight patients switched from CBZ-CO to CBZ-CR. CBZ-CR is therefore a valuable alternative to CBZ-CO.