Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases. Little is known on cerebral perfusion in the general population, as most measurement techniques are too invasive for application in large groups of healthy individuals. Total cerebral blood flow (tCBF) can be noninvasively measured by magnetic resonance imaging (MRI) but is highly correlated with brain volume. We calculated total brain perfusion by dividing tCBF by brain volume, and we investigated determinants of total brain perfusion in comparison with tCBF. Secondly, we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions (WML). This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study, a population-based cohort study. We performed two-dimensional (2D) phase-contrast MRI for tCBF measurement. Brain volume and WML volume were quantitatively assessed. Cardiovascular determinants were assessed by interview and physical examination. We assessed associations between cardiovascular determinants and flow measures with linear regression models, adjusted for age and sex. Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models. We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values. Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion. Prospective studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage, manifested by WML, leads to brain hypoperfusion.