Recently, P/Q-type Ca²⁺ channels have been shown to be involved in neurotransmission in the central nervous system in mammals. We evaluated the effects of the P/Q-type Ca²⁺ channel blocker ω-agatoxin IVA (ω-Aga-IVA) on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery (MCA) occlusion in rats. Intracerebroventricular (i.c.v.) treatment with ω-Aga-IVA significantly attenuated the postischemic increase of brain water content. ω-Aga-IVA also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. ω-Aga-IVA (30 pmol, i.c.v.), which exhibited a neuroprotective effect, had no significant effect on the magnitude of intra- and postischemic brain temperature when compared with vehicle-treated rats. This indicates that the postischemic neuroprotective effect of ω-Aga-IVA is produced by a direct and not an indirect effect via hypothermia. These results suggest that P/Q-type Ca²⁺ channels may be involved in the development of focal ischemic brain injury and that blockers of these channels may be therapeutically useful against ischemic injury.