Introduction: Introduction. Polytherapy with three antiepileptic drugs (AEDs) is used in patients who have seizure episodes classified by physicians and neurologists as refractory or drug-resistant. Although doctors can prescribe these patients 25 various AEDs, no algorithms are available which allow them to choose the most efficacious combinations of AED. Objective: The aim of this study was to isobolographically classify interaction among three classical AEDs (carbamazepine, phenobarbital and valproate), applied in the fixed-ratio combination of 1:1:1, in the maximal electroshock-induced seizures in mice. Material and methods: The anti-seizure activity of the mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) was determined in maximal electroshock-induced seizures – an experimental model of tonic-clonic seizures in mice using type I isobolographic analysis. Results: The mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) produced additive interaction in the maximal electroshock-induced seizure model in mice. The experimentally-derived median effective dose (ED50 exp value) for the mixture was 94.35 mg/kg, whereas the theoretically additive median effective dose (ED50 add value) amounted to 116.77 mg/kg. Conclusions: Although the combination of carbamazepine, phenobarbital and valproate exerted additivity in the mouse maximal electroshock-induced seizure model, it could be recommended for the treatment of patients, if the results of this study would be directly transposed to clinical settings.