The vulnerability of the CA2 sector to chronic exposure to bicuculline was investigated in rat hippocampal slice cultures. Selective neuronal cell death was observed only in the CA2 sector after exposure to 6 microM bicuculline for 12 h, but the effect of the cell toxicity extended to the CA3 sector after 24 h. The effect was increased by adding 20 microM roscovitine but was reduced by adding 200 nM omega-agatoxin IVA. Bicuculline also induced a calcium influx into neuronal cells mainly in the CA2 sector. These results suggest that CA2 is the most vulnerable sector to bicuculline exposure in hippocampal slice cultures, and that neuronal cell death in the CA2 sector involves the P/Q-type voltage-dependent calcium channel.