The present study aimed to elucidate sPLA(2) activity in the normal and kainate-lesioned hippocampus using selective inhibitors of sPLA(2). In normal rats the highest levels of sPLA(2) were observed in the hippocampus, pons, and medulla, followed by the cerebral neocortex and caudate nucleus. After intracerebroventricular kainate injections an increase in total PLA(2) activity was observed in the rat hippocampus. Using a selective sPLA(2) inhibitor 12-epi-scalaradial, sPLA(2) activity was found to be significantly increased by 2.5-fold on the side of the intracerebroventricular injection compared to the contralateral side. A peptide P-NT.II, derived from the amino acid sequence of "PLA(2)-inhibitory protein," discovered in the serum of the reticulated python, also showed potent sPLA(2) inhibitory activity in homogenates from the kainate-injected hippocampus. These results show that there is a high level of sPLA(2) activity in the normal hippocampus, pons, and medulla oblongata, and that the level increases further in the hippocampus after kainate-induced excitotoxic injury. The increased PLA(2) activity was inhibited by P-NT.II, indicating a potential use of this peptide as a PLA(2) inhibitory agent in the brain.