This initial study examines cognitive function in individuals with asymptomatic orthostatic hypotension. Cerebral hypoperfusion accompanying repeated episodes of orthostatic hypotension may eventually produce some cerebral structural deterioration which, depending on foci, could compromise cognitive function. Subjects (aged 55 to 74 years) were relatively healthy women and men, the majority of whom were being treated for non-insulin-dependent diabetes mellitus. Blood pressure (BP) and pulse were measured under supine and upright posture. The difference between BP and pulse under supine and standing conditions indexed orthostatic hypotension. About 1 hr after evaluation of orthostatic hypotension, cognitive testing was performed with individuals comfortably seated. Results showed that, irrespective of possible confounders, including depression, decreased systolic BP in response to upright posture predicted slower reaction times and compromised serial list learning, although sparing immediate and working memory. Orthostatic hypotension, measurable in more than 4% of the elderly, is a hitherto unexplored source of cognitive decline.