Serum of normal volunteers and serum of epileptic patients receiving either a single drug or combined antiepileptic therapy with Phenytoin (Phen); Carbamazepine (Cbz); Primidone (Prim); Phenobarbital (Phb) were examined and showed: No differences with regard to total proteins, albumins and A/G ratio. The alpha 1-globulin fraction increased to 4.4% with Phen/Cbz (P less than 0.001) and decreased to 1.7% with Phen/Prim = (P less than 0.001). The alpha 2-globulins corresponded to 7.2% (P less than 0.001) with Phen/Prim and 15.5% (P less than 0.001) with Phen/Phb treatments. beta-Globulins decreased to 7.1% (P less than 0.05) when received Phen/Phb treatment. Low concentrations of serum gamma-Globulins were found in Phb (P less than 0.001), Prim (P less than 0.001, Phen (P less than 0.001) treated patients. However, with Cbz, Phen/Phb, Phen/Prim this electrophoretic fraction remained within the upper range of normal. IgA of patients treated with Phen showed a mean of 60 mg/dl. Those patients with Phen serum levels below or above 12-20 micrograms/ml remained normal. Prim and Phb treatment also decreased IgA. IgD was normal in patients treated with Phen/Prim. Alterations of immune humoral responses to all antiepileptic drugs were found.