Regional cerebral blood flow (rCBF) was measured by 133Xe inhalation in 46 normal volunteers, aged 21 to 63 years, and 14 neurologically asymptomatic subjects above age 40 with risk factors for atherothrombotic stroke, including hypertension, diabetes mellitus, and hyperlipidemia. In normal volunteers, there was diffuse and progresive reduction of gray matter flow and weight as well as increases of cerebrovascular resistance (CVR) with advancing age. Reduction of gray matter flow with advancing age appears to be attributed in part to neuronal atrophy and in part to cerebral arteriosclerosis. Regional increases of CVR and reduction of gray matter flow with advancing age were most evident in the middle cerebral arterial (MCA) distribution and were enhanced by the association of risk factors. Development of cerebral arteriosclerosis with age and/or risk factors appears to be most evident in MCA distribution.