A challenge paradigm was designed to test the functional sensitivity to anticholinergic agents in Alzheimer's disease. Ten patients with dementia of the Alzheimer type were serially administered three different intravenous doses of the centrally active anticholinergic drug scopolamine and placebo. Testing was carried out in a placebo-controlled, double-blind fashion to measure cognitive, physiologic and behavioral changes. Alzheimer patients showed a marked, dose-related behavioral and cognitive sensitivity to temporary cholinergic blockade. Scopolamine testing may serve as an index of the status of central cholinergic functional integrity, and ultimately may prove useful as a diagnostic or staging test in the evaluation of the cholinergic system in dementia. Research is currently under way with elderly age-matched controls and populations with other neuropsychiatric disorders to explore this hypothesis further.