Bcl-2, a cell death suppressor protein, is expressed during brain development but is largely down-regulated in the adult central nervous system. We previously reported strong expression of bcl-2 in small, "oligodendrocyte-like" cells (OLC) found in glioneuronal hamartias. These hamartias are microscopic cell rests found in temporal lobe resections from patients with intractable epilepsy and are considered a form of cerebral microdysgenesis. However, a causative relationship between these rests and seizures is not clear. We now report the identification, lineage characterization, and postnatal ontogeny of hamartia-like cell rests in temporal lobes of nonepileptic humans. Postmortem temporal lobes from 28 patients without history of neurologic disease (mean age = 53 years; range = 20 to 83 years) were studied. Microscopic cellular aggregates containing immature-appearing, bcl-2-immunoreactive cells (BIC) (identical to OLC) were observed in 23 of 28 (82%) temporal lobes from nonepileptic individuals. BIC were strongly immunoreactive for neuronal-specific class III beta tubulin, neuronal nuclear antigen, and MAP-2, but were consistently negative for neurofilament proteins and Ki67. Such cells were localized to subventricular regions of the caudal amygdala and often extended into the adjacent subcortical white matter and periamygdaloid cortex. BIC became less abundant with advancing age. These findings suggest that hamartia-like rests containing immature postmitotic neurons are normally present in the human brain and that glioneuronal hamartias may not always represent a maldevelopmental lesion associated with epilepsy.