Histamine levels in different regions of the brain in the primate Macaca Radiata were studied following experimental infarction induced in the basal ganglia by coagulation of the middle cerebral artery. In the basal ganglia an elevation of histamine level was seen probably due to proliferation of mast cells. In the hypothalamus, a main constituent of the ascending histaminergic neuronal pathway, a sharp rise in histamine content occurred in infarcted as well as sham-operated animals: this probably reflects non-specific stress-related alterations. In contrast, the cortical area of the ischemic hemisphere showed a higher elevation of histamine, demonstrating that infarction in one region can cause widespread specific changes in histaminergic systems remote from the infarct. The rise in histamine level at the ischemic site could evoke an increase in microcirculation which might aggravate cerebral edema, while changes in the remote regions may be responsible for some of the neurological deficits following stroke.