Rheb is a recently identified member of the Ras super-family and is an immediate early gene that is rapidly and transiently induced in the hippocampal granule cells by NMDA-dependent synaptic activity in the long term potentiation paradigm. The close homologies with Ras and its rapid inducibility strongly suggest that Rheb shares many biochemical and signaling properties with Ras. The present study investigated the effect of middle cerebral artery (MCA) occlusion on the expression of Rheb mRNA in the rat brain. In situ hybridization autoradiography showed that Rheb mRNA was induced in the extensive regions of cerebral cortex and medial striatum surrounding the ischemic region and bilateral hippocampal formation following MCA occlusion. The induction of Rheb mRNA in the cingulate cortex persisted prominently at 24 h of MCA occlusion. Although the Rheb mRNA induction in the medial striatum and hippocampal formation decreased after 8h of occlusion, it still remained significant at 24h of occlusion. The data suggest the possibility that Ras signaling pathways can be implicated in the cerebral ischemia-elicited events through NMDA receptor activation.