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Arterial shear stress is a potent stimulus to vascular adaptation in humans. Typically, increases in retrograde shear have been found to acutely impair vascular function while increases in antegrade shear enhance function. We hypothesized that blood flow and shear stress through the brachial and carotid arteries would change in a similar manner in response to water immersion, an intervention which modifies hemodynamics. Nine healthy young male subjects were recruited to undergo controlled water immersion in a standing upright position to the level of the right atrium in 30°C water. Diameters were continuously and simultaneously recorded in the brachial and common carotid arteries along with mean arterial pressure (MAP), cardiac output (CO), and heart rate before, during, and after 10 min of immersion. MAP and CO increased during water immersion (baseline vs. 8-10 min; 80 ± 9 vs. 91 ± 12 mmHg; and 4.8 ± 0.7 vs. 5.1 ± 0.6 L/min, P < 0.01 and P < 0.05, respectively). We observed a differential regulation of flow and shear stress patterns in the brachial and carotid arteries in response to water immersion; brachial conductance decreased markedly in response to immersion (1.25 ± 0.56 vs. 0.57 ± 0.30 mL.min/mmHg, P < 0.05), whereas it was unaltered in the carotid artery (5.82 ± 2.14 vs. 5.60 ± 1.59). Our findings indicate that adaptations to systemic stimuli and arterial adaptation may be vessel bed specific in humans, highlighting the need to assess multiple vascular sites in future studies.