Hippocampal sclerosis is a complex combination of neuronal and glial changes. It is frequently associated with temporal lobe epilepsy. Six hippocampal specimen were obtained from patients operated on for intractable mesial temporal lobe epilepsy. Comparisons were made with six autopsy controls. The neuronal and glial cells populations were studied by morphometric quantitative analysis. The glial cell types were identified by immunohistochemistry procedures. Distribution of the central (neuronal location) and the peripheral (glial location) benzodiazepine (BZ) binding sites was studied by quantitative autoradiography using [3H]-flumazénil and [3H]-PK11195 as respective ligands. Neuronal death and glial proliferation with the usual HS pattern were confirmed in all cases. Microglial cells, labelled with KP1 antibody (resident component) and with HLA-DR alpha (reactive component) were qualitatively similar in patients and controls. Particular radial organization of numerous, long and thin astrocytic processes, as labelled with GFAP antibody, was observed in the molecular layer of the dentate gyrus in 5 cases. These fibrillary processes were intermingled with the granule cells, which were markedly dispersed in 4 of the cases. In comparison with control group, all the epileptic cases had significant selective decreased central-type and increased peripheral-type BZ receptor. These results were respectively correlated with neuronal loss and glial proliferation. Morphologic results suggest that a specific configuration of astrocytic cell processes may be associated with some of the neuronal changes of human HS. Such aspect has not been reported in the astroglial growth observed in animal models of limbic epilepsy. The lack of reactive microglia suggested the absence of recent cell death.(ABSTRACT TRUNCATED AT 250 WORDS)