In the very old, there is an increased prevalence of immunologically mediated vascular disease. Vascular heparan sulfate proteoglycan (vHSPG) is a molecule which plays an important structural and functional role in the vasculature. Autoimmunity to vHSPG may play a role in the pathogenesis of vascular disease. The presence of autoantibodies to vHSPG was investigated in sera from aged nursing home patients who have a high prevalence of vascular disease. The results showed an association of the presence of autoantibodies to vHSPG in the sera from patients in this aged population with vascular disease, particularly cerebrovascular disease, renal disease and diabetes. In addition, autoantibodies to vHSPG protein core were associated with cerebrovascular disease in this frail elderly population. These studies support the hypothesis that autoimmunity may play a role in vascular disease in the aged.