Urban, minority communities are disproportionately affected by the chronic diseases associated with autonomic neuropathy; however validated measures of autonomic symptoms have not been studied in these complex populations. We sought to validate the Autonomic Symptom Profile (ASP) in a low income, medically complex, urban patient population. Ninety-seven adults were recruited from the outpatient neurology clinic of an academic medical center serving the East Harlem neighborhood of New York City. Participants completed the ASP, and underwent a comprehensive neurologic examination, and a standardized battery of autonomic function tests (quantitative sweat testing, heart rate response to deep breathing (HRDB), Valsalva maneuver, and tilt table). Burden of chronic disease was summarized using the Charlson co-morbidity index (CCI), and detailed medication history was obtained. The ASP displayed good internal consistency (Cronbach's α=.88), even among lower literacy participants. In univariate analyses, the ASP was correlated with HRDB (r=-.301, p=.002), a marker of cardiac autonomic neuropathy, with the CCI (r=.37, p<.001), and with use of medications with autonomic effects [t(95)=-2.13, p=.036]. However, in multivariate analysis, only the CCI remained significant. In this urban, predominantly minority patient population, the symptoms captured by the ASP were more closely associated with burden of medical disease than with autonomic dysfunction. Due to this lack of specificity, it is essential that results from autonomic questionnaires be interpreted in the context of the neurologic history and exam, burden of co-morbid illness and medications, and most importantly autonomic function tests.