Although both morphologic cerebral damage and cognitive dysfunction are known to occur in patients on chronic hemodialysis (CHD) their extent and possible relation have been rarely studied. We therefore performed magnetic resonance imaging of the brain and neuropsychological testing in 30 consecutive CHD patients (mean age 58 years; range 37-69) and in an equal number of asymptomatic volunteers matched for age, sex and major cerebrovascular risk factors. Twenty-four (80%) of the CHD patients were demented according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IIIR and their mean scores on the Mini Mental State Examination (22.9 +/- 4 vs. 27.9 +/- 1.4; p < 0.001) and Mattis Dementia Rating Scale (112.3 +/- 21.5 vs. 141.9 +/- 2.3); p < 0.001) were significantly lower than those of controls. The brains of CHD patients showed significantly more atrophy on visual rating and semiquantitative morphometric measures. Multiple lacunes or confluent white matter hyperintensities predominated in 10 (33%) patients, three showed territorial infarcts and two a combination of both. Clinically these findings were unexpected in almost half of individuals. Marked cognitive impairment was associated with more extensive enlargement of the third ventricle (5.8 +/- 1.8 vs. 7.3 +/- 2 mm; p < 0.04) and the temporal horns (3.5 +/- 1.6 vs. 5.1 +/- 1.8 mm; p < 0.02) but not with the presence of cerebral ischemic lesions or any difference in laboratory data. These results call attention to a very high rate of cerebral damage in individuals undergoing CHD and suggest brain degeneration of probably toxic-metabolic etiology to be associated with severe cognitive impairment of these patients.