We studied the production of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) 2 and 7 days following status epilepticus (SE), induced in rats by intra-amygdala injection of kainate. At day 2 the release of both cytokines by hippocampal slices prepared from epileptic animals was increased compared to controls, whereas at day 7 only TNF alpha secretion was enhanced. Since SE-induced neuronal damage is probably due to excitotoxicity, we investigated the effects of agonists of glutamate receptors on TNF alpha release in organotypic hippocampal cultures. A correlation was found between the damage intensity and the release of TNF alpha, suggesting production of this cytokine by macrophagic microglia. We propose a role for TNF alpha and IL-6 in the adaptive phenomena which follow severe limbic seizures.