Apoptosis of granular cells in the dentate gyrus frequently occurs in animal models of bacterial meningitis. In 37 autopsy cases of bacterial meningitis we evaluated, by light microscopy and in-situ tailing, whether this pattern of neuronal damage is of relevance in humans. Neuronal apoptoses in the dentate gyrus (density 1 to 19/mm2) were observed in 26 cases of bacterial meningitis and in none of 10 aged-matched control cases dying from non-neurological diseases. The density of apoptotic neurons depended on the interval between the onset of symptoms of meningitis and death (death within the first 2 days: 1.8+/-2.8 apoptoses/mm2; later than 18 days: 1.8+/-1.7/mm2; compared to death between days 3 and 18: 7.4+/-6.6 apoptoses/mm2, p = 0.007 and 0.004, respectively). Neuronal apoptosis in the dentate gyrus was not linked to neuronal damage in other parts of the brain or previous treatment with corticosteroids. Since learning deficits are frequently observed in survivors of bacterial meningitis, strategies to reduce the density of apoptotic neurons in the dentate gyrus may decrease the frequency of neurological sequela in patients surviving bacterial meningitis.