A method was devised to measure gray and white matter cerebral blood flow simultaneously in multiple regions of the brain using133Xenon and a multiple-crystal scintillation camera. Following magnification cerebral arteriography,133Xe was injected into the internal carotid artery and the washout of tracer was monitored with a scintillation camera which consists of 294 individually collimated NaI (TI) crystals. These data, obtained from each crystal overlying the brain, were processed by a weighted least-squares nonlinear regression technique. The blood flow rates of the rapid and slow compartments were calculated by the Kety-Schmidt formula along with 95% confidence limits for each measurement.In four patients, local increases or decreases in regional cerebral flow were correlated with areas of pathology. In one patient with a cerebral arteriovenous malformation, regions of local shunting of tracer were identified. Application of a three-compartment analysis to these curves permitted estimation of the magnitude of shunting along with gray and white matter flow in the lesion. The increased discrimination provided by the multiple-crystal camera and the estimates of measurement accuracy obtained by this mathematical analysis may facilitate more precise localization of regional blood flow abnormalities in intracranial disease.