OBJECTIVES: To investigate differences in hemodynamic profile between hyperadrenergic and non-hyperadrenergic postural orthostatic tachycardia syndrome (POTS) in response to head-up tilt test (HUTT). METHODS: Ten patients with hyperadrenergic and 33 patients with non-hyperadrenergic POTS underwent HUTT consisting of a 10-min supine phase and 30-min 70 degrees tilted phase. Heart rate (HR), systolic and diastolic blood pressure (dBP), and heart rate variability (HRV) parameters of the two groups were compared. RESULTS: Hyperadrenergic patients had higher supine HR (82.6 +/- 16.3 bpm vs. 73.8 +/- 10.4 bpm, p=0.048). Supine HRV analysis showed significantly lower cardiac vagal activity and possible predominance of cardiac sympathetic activity in the hyperadrenergic group. Non-hyperadrenergic patients had lower dBP during the first four minutes of tilt. Furthermore, 60% of non-hyperadrenergic patients had lower average dBP in the 1st minute of tilted phase when compared to supine values, whereas only 2 of 10 hyperadrenergic patients exhibited the same response. Syncope or intolerable symptoms, causing early ending of HUTT, developed earlier in the non-hyperadrenergic group (8.9 +/- 6.8 min vs. 21.2 +/- 3.5 min, p=0.001). CONCLUSION: Hyperadrenergic and non-hyperadrenergic type of POTS seem to have distinctly different response to HUTT. SIGNIFICANCE: This study has shown significant differences in hemodynamic response to HUTT between hyperadrenergic and non-hyperadrenergic type of POTS indicating possible differences in their pathophysiology.