Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 μm). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces.