The infusion of physiological salt solution into the lumen of ring segments of the isolated rabbit facial vein induces an increase in vessel wall tone. Changes in <sup>22</sup>Na<sup>+</sup> and <sup>45</sup>Ca<sup>2+</sup> net uptake as well as <sup>22</sup>Na<sup>+</sup> unidirectional efflux in response to flow in this vessel were compared to the response to histamine (1 µ M) and to angiotensin II (0.1 µ M). <sup>22</sup>Na<sup>+</sup> net uptake per unit force developed in response to flow was 7.9-fold greater than that for histamine (1 µ M) and twice that for angiotensin II (0.1 µ M). In comparison, <sup>45</sup>Ca<sup>2+</sup> net uptake per unit force in response to flow, histamine and K<sup>+</sup> were similar. Flow-induced contraction and the related <sup>45</sup>Ca<sup>2+</sup> and <sup>22</sup>Na<sup>+</sup> net uptake were decreased by amiloride (30 µ M) and methyl isobutyl amiloride (30 µ M) without changes in <sup>45</sup>Ca<sup>2+</sup> or <sup>22</sup>Na<sup>+</sup> net uptake per unit force. Ouabain (10 µ M) enhanced flow-induced contraction and the related <sup>22</sup>Na<sup>+</sup> net uptake. Both ouabain (10 µ M) and Bay K 8644 (1 µ M) increased flow-induced contraction and the related <sup>45</sup>Ca<sup>2+</sup> net uptake whereas they decreased the <sup>45</sup>Ca<sup>2+</sup> net uptake per unit force. Flow, histamine and angiotensin II increased the unidirectional efflux of <sup>22</sup>Na<sup>+</sup>. This increase in <sup>22</sup>Na<sup>+</sup> unidirectional efflux was attenuated by ouabain (10 µ M). These experiments demonstrate that the increases in wall force due to flow, histamine and angiotensin II are associated with increases in <sup>22</sup>Na<sup>+</sup> net uptake and unidirectional efflux. Flow preferentially promotes the entry of Na<sup>+</sup>, compared to histamine and angiotensin II.