Little is known about the neurochemical pathology of vascular dementia (VD); it was suggested that cholinergic mechanisms play a role in the pathogenesis of VD, as well as been established for Alzheimer's disease (AD). A recently devised test of motor cortex excitability, the short latency afferent inhibition (SAI), has been proven to depend upon the activity of cholinergic circuits in the human brain. To evaluate, in vivo, the functional role of the cholinergic system in the cognitive dysfunction associated with VD, we used this test in 20 patients with subcortical ischemic VD (SIVD) and in 25 control subjects. Mean SAI was significantly reduced in the SIVD patients; however, individual data varied widely, with SAI responses ranging from normal to markedly reduced values. These findings provide physiological evidence for an important role for cholinergic mechanisms in the pathogenesis of VD. The evaluation of SAI, similar to that described in AD patients, could help in identifying those patients who are more likely to respond to treatment with cholinergic drugs.