Cerebral white matter hyperintensities on brain MRI (leukoaraiosis) are associated with increased risk of stroke and dementia. To assess the relationships of blood pressure level and circadian pattern with leukoaraiosis, we obtained 24-hour ambulatory blood pressure recordings and brain magnetic resonance images in 343 white and 267 black adults who were members of sibships that had >or=2 siblings with essential hypertension. In multiple linear regression models, factors associated with greater leukoaraiosis in both racial groups included age (P<or=0.002), homocysteine levels (P<or=0.006), and brain volume (P<or=0.008). In blacks, ambulatory blood pressure measures associated with greater leukoaraiosis were higher awake, asleep, and 24-hour systolic and diastolic levels (P<or=0.009 for each). In addition, there was a trend for smaller nocturnal declines in systolic and diastolic levels (ie, nondipping patterns) to be associated with greater leukoaraiosis, and all of these associations, except nondipping of diastolic level, remained or became significant after controlling for office blood pressure (P<0.05 for each). In whites, among ambulatory blood pressure measures, only higher asleep diastolic levels trended toward association with greater leukoaraiosis. However, similar to findings in blacks, nondipping of systolic and diastolic ambulatory blood pressure levels were each associated with greater leukoaraiosis (P<or=0.008), and all of these associations remained or became significant after controlling for office blood pressure (P<or=0.009 for each). Higher ambulatory blood pressure levels and a nondipping circadian pattern contribute to greater leukoaraiosis volume after controlling for office blood pressure.