Significant increases in serum levels and decreases in hair copper levels have been previously described in epileptic patients treated with anticonvulsant drugs. A condition not directly related to copper nutriture, such as chronic treatment with these drugs, could increase the serum concentrations of copper and ceruloplasmin and would mask a possible copper deficiency produced by drug-increased biliary copper excretion. Serum immunoreactive ceruloplasmin concentration and its oxidase activity were determined in 90 adult epileptic patients treated with phenobarbital (n=60), phenytoin (n=70), carbamazepine (n=33) and valproic acid (n=8). The levels of ceruloplasmin and oxidase activity were significantly higher (P<0.001) than in an age and gender-matched control group (n=49). The significant correlations (P<0.01) between ceruloplasmin and the urinary excretion of D-glucaric acid, serum gamma-glutamyltransferase (GGT) and drug score in the patients group, would suggest that phenobarbital-type enzyme-inducing agents may increase the hepatic synthesis of ceruloplasmin. In 11 patients with a beta-globulin migrating GGT isoform (GGT3), a sensitive marker of cholestasis, the levels of ceruloplasmin, oxidase activity and total GGT activity were significantly higher (P<0.05) than in the group of 79 patients without the GGT3 isoform; consequently, in some cases a drug-induced cholestasis may also contribute to the increase of serum copper and ceruloplasmin. The values obtained for the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) suggest that in the most of the cases, chronic administration of phenobarbital, phenytoin, carbamazepine or valproic acid, does not produce marginal or moderate copper deficiency.