Background. White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. Method. T2- weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. Results. After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. Conclusion. An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.