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 22Na+ and 45Ca2+ net uptake as well as 22Na+ unidirectional efflux in response to flow in this vessel were compared to the response to histamine (1 µM) and to angiotensin II (0.1 µM). 22Na+ net uptake per unit force developed in response to flow was 7.9-fold greater than that for histamine (1 µM) and twice that for angiotensin II (0.1 µM). In comparison, 45Ca2+ net uptake per unit force in response to flow, histamine and K+ were similar. Flow-induced contraction and the related 45Ca2+ and 22Na+ net uptake were decreased by amiloride (30 µM) and methyl isobutyl amiloride (30 µM) without changes in 45Ca2+ or 22Na+ net uptake per unit force. Ouabain (10 µM) enhanced flow-induced contraction and the related 22Na+ net uptake. Both ouabain (10 µM) and Bay K 8644 (1 µM) increased flow-induced contraction and the related 45Ca2+ net uptake whereas they decreased the 45Ca2+ net uptake per unit force. Flow, histamine and angiotensin II increased the unidirectional efflux of 22Na+. This increase in 22Na+ unidirectional efflux was attenuated by ouabain (10 µM). These experiments demonstrate that the increases in wall force due to flow, histamine and angiotensin II are associated with increases in 22Na+ net uptake and unidirectional efflux. Flow preferentially promotes the entry of Na+, compared to histamine and angiotensin II.