We have previously demonstrated that expression of epidermal growth factor receptor (EGFR) was upregulated on vascular endothelial cells from brains of patients with dementia but not in brains from non-demented patients. The present study used a monoclonal antibody against EGFR to examine its expression in pituitary gland, scalp, abdominal skin and brain of 29 patients with and without various dementias and neurological deficits, as well as normal aged controls. Of 20 clinically demented patients examined postmortem, 15 exhibited EGFR immunoreactivity (IR) on brain and peripheral vascular endothelial cells. Examination of nine non-demented patients revealed only 1 patient with EGFR-IR. EGFR-IR was expressed on all blood vessels, regardless of size or location within the tissue examined. Ultrastructural analysis of EGFR revealed that in pituitary, like brain, the receptor was restricted to the lumenal cell surface of vascular endothelial cells. In all cases of EGFR-IR there was an absolute correlation between central nervous system and peripheral expression; if there was EGFR-IR in brain vessels it was present in skin. If there was no staining in brain there was no peripheral skin vessel staining; and vice versa. Increased EGFR expression may indicate proliferative or regenerative changes in the vasculature of affected patients and may provide a biological marker supporting the diagnosis of dementia by analysis of skin biopsy.