Fifteen patients with Alzheimer's disease (AD) and 16 age-matched controls underwent skin vessel reactivity tests employing three vasodilating substances with different modes of action: acetylcholine (ACh), nitroprusside, and isoprenaline. The substances were iontophoresed into the skin and the results were mapped through a newly developed laser Doppler perfusion imager. The skin vascular responses of the patients to ACh and isoprenaline but not nitroprusside were significantly attenuated compared to those of the controls. The differences between patient and control groups concerning skin vessel reactivity might be due to receptor/signal transduction abnormalities but might in addition indicate an attenuated endothelium-dependent vasodilation in AD. The results of this study support the hypothesis that AD might be a systemic disease. They suggest that tests of skin vessel reactivity might be of help in the antemortem diagnosis of AD.