Postural tachycardia syndrome (POTS) is characterized by exercise intolerance and sympathoactivation. To examine whether abnormal cardiac output and central blood volume changes occur during exercise in POTS, we studied 29 patients with POTS (17-29years) and 12 healthy subjects (18-27 years) using impedance and venous occlusion plethysmography to assess regional blood volumes and flows during supine static handgrip to evoke the exercise pressor reflex. POTS was subgrouped into normal and low flow groups based on calf blood flow. WE examined autonomic effects with variability techniques. During handgrip systolic BP increased from 112±4 to 139±9 mmHg in control from 119±6 to 143±9 in normal flow POTS, but only from 117±4 to 128±6 in low flow POTS. Heart rate increased from 63±6 to 82±4 bpm in control, 76±3 to 92±6 in normal flow POTS, and 88±4 to 100±6 in low flow POTS. Heart rate variability and coherence markedly decreased in low flow POTS indicating uncoupling of baroreflex heart rate regulation. The increase in central blood volume with handgrip was absent in low flow and blunted in normal flow POTS associated with abnormal splanchnic emptying. Cardiac output increased in control, was unchanged in low flow and was attenuated in normal flow POTS. Total peripheral resistance was increased compared to control in all POTS. The exercise pressor reflex is attenuated in low flow POTS. While increased cardiac output and central blood volume characterizes controls, increased peripheral resistance with blunted or eliminated i central blood volume increments characterize POTS and may contribute to exercise intolerance.