We have measured the relaxation of rat mesenteric small arteries (internal diameter ca. 200 µm) from a potassium contracture under conditions where the transplasmalemmal sodium gradient was altered. Adjustment of the sodium gradient was made either by exposing vessels to ouabain (1 mM) for different periods to vary the intracellular sodium concentration (Na<sub>i</sub>), or by varying the sodium concentrations of the relaxation solutions (Na<sub>o</sub>). Under normal conditions (where we have previously shown Na<sub>i</sub> is about 19 m M), vessels relaxed completely within 1 min in low sodium solutions (Na<sub>o</sub> = 25 m M) using either sucrose, choline-Cl or MgCl<sub>2</sub> as substitutes. However, the relaxation (measured after 1 min) was reduced when sucrose substitution was used, and further experiments were made using this substitute. Here it was found that exposing vessels to ouabain, for example 90 min (thus increasing Nai to about 73 m M) and then performing the relaxation in a low sodium solution gave only about 50% relaxation after 1 min. Experiments with intermediate sodium concentrations in the relaxation medium showed that reduction to 100 m M had no significant effect on the relaxation, and that it was only below 50 mM that effects were most marked. The effects of altered sodium gradient were eliminated if the calcium concentration of the relaxation medium was zero. The results indicate that under normal physiological conditions, small changes in sodium gradient have little effect on calcium metabolism of rat mesenteric small arteries, but also that under extreme conditions net calcium extrusion does appear to be reduced by a reduced sodium gradient.