Chronological changes of [H-3]inositol 1,4,5-trisphosphate (IP3) binding sites were determined after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. One day after the ischemia, [H-3]IP3 binding sites decreased significantly compared with the control values in the lateral segment of the caudate putamen and the cerebral cortex, both supplied by the occluded MCA. Moreover, 3 days after the ischemia, a significant decrease of [H-3]IP3 binding sites was observed in the substantia nigra of ischemic side. In the ipsilateral thalamus, however, there was no alteration until 1 week after the ischemia, and then [H-3]IP3 binding sites increased significantly 2 weeks (P < 0.05) and 4 weeks (P < 0.01) after the ischemia. Based on the present study, we speculate that different mechanisms associated with signal transduction systems may be responsible for exo-focal postischemic delayed neuronal changes in the thalamus and the substantia nigra. The increase of [H-3]IP3 binding sites of the thalamus in the chronic stage may be new evidence of plasticity related to neurotransmission.