Dyspnea is a common symptom in patients with pulmonary and cardiac disease. Orthostatic hypotension is rarely considered a cause of dyspnea. We reviewed the medical records of 651 consecutive patients referred for the evaluation of dysautonomia to investigate the prevalence of dyspnea and its association with OH and other autonomic abnormalities. Dyspnea was reported by questionnaire in 30% of patients with OH, compared to 10% of age and sex matched patients without OH (P<0.05, chi(2)). There was a trend toward earlier blood pressure falls in patients with dyspnea. During autonomic testing, 25% of patients (10 of 40) with OH who reported dyspnea on the questionnaire had shortness of breath coincident with blood pressure falls during tilt table and active standing. The time to maximal blood pressure fall was shorter in patients with OH who experienced shortness of breath during testing compared to those without dyspnea (11 minutes vs. 21 minutes, P<0.05). In this study, dyspnea was frequently associated with OH. Ventilation perfusion mismatch, due to inadequate perfusion of ventilated lung apices may be the most likely underlying cause of orthostatic dyspnea in patients with OH.