We examined the role of cholinergic system in multi-infarct dementia (MID) by measuring acetylcholinesterase (AChE) activities in cerebrospinal fluid (CSF) of clinically diagnosed MID patients, Alzheimer's disease (AD) patients and controls. In spite of the similar clinical severity of dementia, MID patients had unaltered AChE levels, whereas AD patients had significantly reduced AChE levels in CSF when compared to controls. In the autopsy study we analyzed choline acetyltransferase (ChAT) levels in four cortical brain areas from clinically and neuropathologically studied AD patients, demented non-AD patients and controls. ChAT activities in the cerebral cortex in non-AD patients were on the same level as in controls, but AD patients had a marked loss of ChAT activity in all four cortical brain areas studied. Although cholinergic deficit is a usual phenomenon associated with cognitive failure, severe dementia can exist without cholinergic dysfunction.