The V.A. Epilepsy Cooperative Study Group evaluated monotherapy with carbamazepine, phenobarbital, phenytoin, and primidone in a total of 622 patients with previously untreated partial seizures. In the 24 months following onset of treatment, 223 patients failed treatment. Analysis of these failures reveals that the majority occurred during the first 6 months with equal contributions to failure from systemic toxicity, neurotoxicity, and seizures. The contribution of systemic toxicity to failure was significantly less in the next 18 months. An increase in the contribution of seizures to failure was seen in this latter period.