Immersion in thermoneutral water increases cardiac output and peripheral blood flow and reduces systemic vascular resistance. This study examined the effects of head-out water immersion on vascular function. Twelve healthy middle-aged males were immersed during 60 min in the seated position, with water at the level of xiphoid. Local and central vascular tone regulating systems were studied during that time. Brachial artery diameter and blood flow were recorded using ultrasonography and Doppler. Endothelial function was assessed with flow-mediated dilation. Results were compared with the same investigations performed under reference conditions in ambient air. During water immersion, brachial artery diameter increased (3.7 ± 0.2 mm in ambient air vs. 4 ± 0.2 mm in water immersion; p < 0.05). Endothelium-mediated dilation was significantly lower in water immersion than in ambient air (10% vs. 15%; p = 0.01). Nevertheless, the difference disappeared when the percentage vasodilatation of the brachial artery was normalized to the shear stimulus. Smooth muscle-mediated dilation was similar in the 2 conditions. Spectral analysis of systolic blood pressure variability indicated a decrease in sympathetic vascular activity. Plasma levels of nitric oxide metabolites remained unchanged, whereas levels of natriuretic peptides were significantly elevated. An increase in brachial blood flow, a decrease in sympathetic activity, a warming of the skin, and an increase in natriuretic peptides might be involved in the increase in reference diameter observed during water immersion. Endothelial cell reactivity and smooth muscle function did not appear to be altered.