The clinical records of 38 cats (1985–1995) with a neuropathologically confirmed diagnosis of necrosis of the hippocampus and occasionally the lobus piriformis were evaluated retrospectively. There was no sex or breed predisposition. Most cats were between 1 and 6 years of age (mean age = 35 months) and had either generalized or complex-partial seizures of acute onset and rapid progression. The seizures had a tendency to become recurrent and to present as clusters or even status epilepticus later in the course of the disease. Fourteen cats died spontaneously, and 24 were euthanized. Histopatologic examination revealed bilateral lesions restricted to the hippocampus and occasionally the lobus piriformis. The lesions seemed to reflect different stages of the disease and consisted of acute neuronal degeneration to complete malacia, affecting mainly the layer of the large pyramidal cells but sometimes also the neurons of the dentate gyrus and the piriform lobe. The clinical, neuropathologic, and epidemiologic findings suggest that the seizures in these cats were triggered by primary structural brain damage, perhaps resulting from exitotoxicity. The cause remains unknown, but epidemiologic analysis suggests an environmental factor, probably a toxin.