In a group of 59 epileptic children treated with Phenytoin (PHT) and valproate sodium (VPA), either alone or in combination, the following effects were studied: (1) the reciprocal effect on the serum levels of the two drugs, and (2) the enzyme-inducing effects of both drugs. VPA had no effect on PHT levels, but PHT significantly decreased VPA concentrations. PHT enhanced both y-glutamyltranspeptidase activity (y-GT) and D-glucaric acid excretion (GLA); these effects were potentiated by VPA. VPA alone did not affect y-GT, but significantly enhanced GLA.