Heat shock proteins (HSPs) are induced by a variety of insults to the nervous system, including seizures, and may be neuroprotective. If this is so, prior induction of HSPs should decrease neuronal damage upon re-exposure to an injurious stimulus. To test this hypothesis in relation to seizures, bicuculline was given to rats in two sessions, separated by 1, 3, 5 or 7 days; seizure activity was recorded, and HSP-like immunoreactivity and neuronal injury (acid-fuchsin staining) were quantified in the CA3c sector of the hippocampus. Prior seizures conferred a time-dependent protective effect against hippocampal injury induced by subsequent seizures, which may represent 'epileptic tolerance', analogous to the previously described phenomenon of 'ischemic tolerance'.