Hippocampal sclerosis is the sole abnormality found in approximately 65% of all temporal lobe specimens resected for intractable temporal lobe epilepsy. Up to 27% of en bloc temporal lobectomy specimens, however, show no definitive pathological changes. The lateral amygdaloid nucleus from 8 consecutive patients who underwent temporal lobectomy in whom no definitive hippocampal pathology was present and corresponding tissue from 8 consecutive patients with hippocampal sclerosis were subjected to quantitative estimation of neuronal density and astrogliosis. As compared to amygdaloid tissue from autopsy control subjects with no history of neurological disease, both the patient group with and that without hippocampal sclerosis consistently exhibited severe neuronal loss and gliosis with no quantitative differences between the two groups. Blinded clinical review of both groups of patients revealed that the development of hippocampal sclerosis was associated with a history of early brain insult; this history was absent in patients with isolated amygdaloid sclerosis. Neuropsychological testing prior to surgery demonstrated that patients with hippocampal sclerosis displayed a greater degree of memory impairment than did those without hippocampal sclerosis. We conclude that amygdaloid sclerosis occurs in the absence of hippocampal sclerosis, and that these patients form a distinct group with no history of early brain insult and milder memory impairment than that seen in patients afflicted with hippocampal sclerosis.