INTRODUCTION: Individuals with tetraplegia have impaired central control of sympathetic vascular modulation and blood pressure (BP); how this impairment affects cerebral blood flow (CBF) is unclear. OBJECTIVES: To determine if persons with tetraplegia maintain CBF similarly to able-bodied controls after a hypotensive challenge. METHODS: Seven individuals with chronic tetraplegia and seven age-matched, non-SCI control subjects underwent a hypotensive challenge consisting of angiotensin-converting enzyme (ACE) inhibition (1.25 mg enalaprilat) and 45 degrees head-up tilt (HUT). Heart rate (HR), low frequency systolic BP variability (LFsbp), brachial mean arterial pressure (MAP) and middle cerebral artery CBF were measured before and after the challenge. Group differences for the baseline (BL) to post-challenge response were determined by repeated measures ANOVA. RESULTS: HR did not differ between the groups in response to the hypotensive challenge. LFsbp response was significantly reduced in the tetra compared to the control group (-38 +/- 51 vs. 72 +/- 93%, respectively). MAP did not differ between the groups at BL but was significantly lower in the tetra compared to the control group post-challenge (55 +/- 13 vs. 71 +/- 9 mmHg, respectively); the percent change in MAP was significantly greater in the tetra than in the control group (-29 +/- 14.1 vs. -13 +/- 9%, respectively). However, CBF did not differ between the groups at baseline or post-challenge; the percent change in CBF post-challenge was not different between the tetra and control groups (-29 +/- 13.2 vs. -23 +/- 10.3%, respectively). INTERPRETATION: Despite impaired sympathetic vasomotor and BP control, CBF in persons with tetraplegia was comparable to that of control subjects during a hypotensive challenge.