We examined the effects of dantrolene, an inhibitor of intracellular calcium release, on hippocampal neuronal damage associated with 140 min of limbic status epilepticus in the rat. Dantrolene (10 mg/kg i.p.) was administered after either 30 min or 140 min of status epilepticus. Early administration was associated with a significant reduction in the amount of neuronal injury in all hippocampal subregions, while late administration was associated with less neuronal injury in area CA3 only. These findings suggest that a substantial portion of seizure-induced hippocampal injury is associated with release of calcium from intracellular stores, and that early administration of dantrolene may be a useful adjunct to anticonvulsant treatment of status epilepticus.