The arterial baroreflex responds to acute reductions in mean arterial pressure (MAP) by eliciting a heart rate response, maintaining MAP at normal levels. In the case of traumatic blood loss, Trendelenburg position (i.e., head-down tilt) is often used clinically to help compensate for reductions in MAP through gravity-dependent shifts in blood volume distribution toward the central cavity, but its use is controversial. A lower-body negative pressure (LBNP) box can be used to study baroreflexes by eliciting acute reductions in MAP through shifts in blood volume distribution toward the lower extremities, reducing venous return. We developed a novel integrated tilt table-LBNP box to investigate the cardiovascular and cerebrovascular effects of head-up and head-down tilt (HUT, HDT) on LBNP-induced hypotension. We hypothesized that 45° HUT would elicit a larger arterial baroreflex heart rate response to acute -50 mm Hg LBNP than supine or 45° HDT. Additionally, we hypothesized that there would be differential cerebral autoregulation (CA) between the middle cerebral artery (MCA) and posterior cerebral artery (PCA) during acute LBNP. 13 male volunteers (BMI 26.4±3 kg/m2; 24.2±4.8 yrs) were recruited. Following familiarization and consent, subjects were instrumented for measurement of instantaneous heart rate (IHR; ECG), MAP (mm Hg; finometer), end-tidal (PET)CO2 (Torr) and MCA and PCA cerebral blood velocity (CBV; cm/s; transcranial Doppler ultrasound). Subjects were placed in the tilt-table-LBNP box in supine position, underwent a 10-min baseline period, and exposed to -50 mmHg of acute LBNP for a maximum of ten minutes. The protocol was then repeated in 45° HUT and HDT in randomized order. Subjects were coached to maintain PETCO2 to resting values (±2 Torr). LBNP was terminated if systolic blood pressure was reduced 30% from resting values (pre-syncope; PS). We found that the arterial baroreflex-mediated IHR responses were linear and tilt-dependent. The slopes of the IHR responses were largest in 45° HUT, but less effective at protecting MAP than in supine and 45° HDT during acute LBNP. 10/13 subjects in 45° HUT reached PS in 427.7s, 3/13 subjects in supine position reached PS in 450.3s and no subjects reached PS in 45° HDT. PETCO2 was unchanged during LBNP in all three positions with coached breathing, eliminating the confounding effects of cerebrovascular CO2 reactivity on CBV. Although MAP was unchanged during LBNP prior to PS in all positions, there were differences between baseline and LBNP MCA in 45° HDT and 45° HUT, but there were no differences in the PCA between baseline and LBNP in any body position. Our findings suggest (a) Trendelenburg may be a useful application to prevent hypovolemic shock, and (b) CA may be different between anterior and posterior cerebral arterial circuits during acute LBNP.