The role of the dentate gyrus (DG) in the development and maintenance of kindling induced by periodic electrical stimulation of the entorhinal cortex (EC) was evaluated in rats. Colchicine, a selective neurotoxin for granule cells of the DG, was injected into the DG: prior to kindling and after the development of kindling. Prior destruction of the DG delayed the development of afterdischarge (AD) induced by EC stimulation, but kindling proceeded at normal rates after the first AD was induced. Destruction of the DG after kindling did not abolish the kindled seizures. Thus, the DG was not required for either the development or maintenance of kindling by EC stimulation, but an intact perforant path input from the EC to DG facilitated the emergence of epileptogenesis by kindling of the EC. The results suggest that kindling develops and is maintained in a network of multiple pathways which are related to the site of stimulation. The DG appears to be the site of a temporally specific alteration which facilitates the development of kindling by EC stimulation.