Recent studies in our laboratory demonstrated that spontaneous breathing through an inspiratory impedance threshold device (ITD) increased heart rate (HR), stroke volume (SV), cardiac output (Q), and mean arterial blood pressure (MAP) in supine human subjects. In this study, we tested the effectiveness of an ITD as a countermeasure against development of orthostatic hypotension, provoked using a squat-to-stand test (SST). Using a prospective, randomized blinded protocol, 18 healthy, normotensive volunteers (9 males, 9 females) completed two-counterbalanced 6-min SST protocols with and without (sham) an ITD set to open at 0.7 kPa (7-cm H(2)O) pressure. HR, SV, Q, total peripheral resistance (TPR), and MAP were assessed noninvasively with infrared finger photoplethysmography. Symptoms were recorded on a 5-point scale (1 = normal; 5 = faint) of subject perceived rating (SPR). The reduction in TPR produced by SST (-35 +/- 5 %) was not affected by the ITD. Reduction in MAP with ITD during the transient phase of the SST (-3.6 +/- 0.5 kPa or -27 +/- 4 mmHg) was less (P = 0.03) than that measured while breathing through a sham device (-4.8 +/- 0.4 kPa or -36 +/- 3 mmHg) despite similar (P < 0.926) elevations in HR of 15 +/- 2 bpm. SV (+2 +/- 4 %) and Q (+22 +/- 5 %) with the ITD were higher (P < 0.04) than SV (-8 +/- 4 %) and Q (+10 +/- 6 %) without the ITD. SPR was 1.4 +/- 0.1 with ITD compared to 2.0 +/- 0.2 with the sham device (P < 0.04). This reduction in orthostatic symptoms with application of an ITD during the SST was associated with higher MAP, SV and Q. Our results demonstrate the potential application of an ITD as a countermeasure against orthostatic hypotension.