A serine proteinase inhibitor, PI-6, is a member of the serine proteinase inhibitor (serpin) superfamily. In the present study, we investigated the developmental expression of PI-6 in the mouse brain and the effect of experimental ischemia on the expression of PI-6 in the adult brain. Northern blot analysis showed a high level of expression of PI-6 mRNA in brain stem and diencephalon as compared with other regions in the adult brain. The expression of PI-6 mRNA in the whole brain was increased gradually until 11 days after birth and was decreased again in the adult brain. In situ hybridization analysis revealed that the mRNA was localized in pyramidal cell layer of the post-natal hippocampus, especially in CA3 region, and in layer V of the cerebral cortex. In the brain stem, two specific motor nuclei, the facial nucleus and the motor nucleus of trigeminal nerve, which are important to active feeding, were strongly positive for PI-6 mRNA. Brain ischemia induced by bilateral ligation of the common carotid artery led to an increase in PI-6 mRNA expression in the whole brain, accompanied by the degeneration of hippocampal pyramidal cells. These results indicate distinct temporal and spatial expression of PI-6 in the mouse brain and suggest the involvement of PI-6 in the maturation of neurons and degenerative and regenerative processes.