Phenylephrine is an alpha-adrenergic agent and yet seems to increase near-infrared spectroscopy determined muscle oxygenation (SmO2) that reflects the ratio between oxygenated (O(2)Hb) and deoxygenated (Hb) haemoglobin/myoglobin. We examined whether the increase in SmO2 by phenylephrine reflects veno-constriction and to secure filling of the veins, subjects were exposed to head-up tilt (HUT). Phenylephrine (0.2 mg) was administered to 10 healthy males (24 years (22-27; median with interquartile range)) during 40 degrees HUT with SmO2, O(2)Hb and Hb determined for the biceps brachii and vastus lateralis muscles. Changes in red cell volume within the thorax and thigh were evaluated by electrical admittance and brachial vein diameter determined by ultrasound. HUT accumulated blood in arms and legs as indicated by reduced thoracic and conversely enhanced thigh electrical admittance. Both over the arm and leg, HUT reduced SmO2 as a consequence of reduced O(2)Hb and increased Hb (p < .05). After 5 min HUT, phenylephrine increased MAP and total peripheral resistance, and both arm and thigh SmO2 increased due to a decrease in Hb and an increase in O(2)Hb. The results confirm that SmO2 decreases during HUT and demonstrate venous filling in the limbs. Furthermore, vasoconstriction during HUT is indicated by a decrease in O(2)Hb. Conversely, phenylephrine increased SmO2 likely illustrating increased muscle blood flow and venoconstriction as O(2)Hb increased while Hb was reduced.