Chronic focal epilepsy is associated with synaptic plasticity and growth of new connections. Brain-derived neurotrophic factor (BDNF) is associated with each of these processes in normal brain and shows acute up-regulation in models of generalized epilepsy. Here, using an experimental model of focal epilepsy, we show persistent up-regulation of BDNF mRNA, independent of that of other growth factors, in association with the development and persistence of chronic seizures. In situ hybridization histochemistry revealed that rats perfused within 2-3 days after seizure onset had widespread increases in BDNF mRNA levels in the neocortex. Rats perfused at later times, however, showed focal up-regulation of BDNF mRNA at the injection site and down-regulation in a surrounding cortical zone. Nerve growth factor and neurotrophin-3 mRNAs were not significantly altered. These reciprocal changes in BDNF gene expression in the epileptic focus and the cortical surround may contribute to plastic changes in epileptic neuronal circuits that accompany the transition from acute to chronic epilepsy. BDNF down-regulation in the surround is likely to be associated with the inhibitory surround that hampers seizure spread, but facilitates the persistence of a chronic epileptic focus.