OBJECTIVE Exaggerated blood pressure (BP) responses to mental stress, an index of autonomic dysregulation, have been related to enhanced risk for stroke. This study examined cross-sectional relations of stress-induced BP reactivity to silent cerebrovascular disease assessed by magnetic resonance imaging (MRI) in healthy older adults. METHODS Sixty-seven nondemented, community-dwelling older adults (ages 55 to 81; 75% male) free of major medical, neurological, or psychiatric disease, engaged in: (1) clinical assessment of resting systolic and diastolic BP; (2) assessment of systolic and diastolic BP responses to 3 laboratory-based mental stressors; and (3) MRI. MRIs were rated for small silent infarcts (> or =3 mm), infarct-like lesions (<3 mm), and periventricular and deep white matter hyperintensities (WMH). RESULTS After adjustment for age, gender, resting clinic BP, and fasting glucose levels, higher systolic BP reactivity was associated with an increased number of small silent infarcts (r2=0.14; P=0.004) and greater severity ratings of periventricular (r2=0.08; P<0.04) and deep WMH (r2=0.06; P<0.05). Higher diastolic BP reactivity was similarly associated with an increased number of small silent infarcts (r2=0.08; P<0.04), and greater severity ratings of periventricular (r2=0.08; P<0.04) and deep WMH (r2=0.11; P=0.009). CONCLUSIONS These results indicate that greater stress-induced BP reactivity is associated with enhanced silent cerebrovascular disease on MRI in healthy asymptomatic older adults independent of resting BP levels. Exaggerated stress-induced BP reactivity warrants further examination as a potential biobehavioral risk factor for cerebrovascular disease.