Morphological white matter changes were investigated in clinically and neuropathologically diagnosed cases of Alzheimer's disease (AD; 60 cases) and vascular dementia (VaD; 40 cases). In 33 of 60 AD cases, a white matter disease (WMD) characterized by tissue rarefaction, mild gliosis and a non-amyloid small-vessel sclerosis occurred in the central, preferentially frontal deep white matter. The mean vessel density was significantly lower than in normal control case frontal white matter. The presence of WMD did not parallel the severity of grey matter Alzheimer encephalopathy. In 25 of 60 AD cases, white matter degeneration with signs of both condensation and rarefaction of tissue elements was seen subjacent to advanced cortical degeneration in the temporal lobes. It concurred with WMD in only 13 cases and was judged to be of anterograde, Wallerian type and not related to angiopathy. In VaD, similar changes occurred, accompanied by several types of focal and topographically related lesions. For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases. For the recognition of such subtle variations in the spectrum of WMD, modern imaging techniques are crucial for detailed clinical diagnosis and attempts at therapeutic intervention.