Small reductions in external sodium ions [(Na+] o), which cause no contractile effects in normal Mg2 (+)-containing medium, cause an immediate contraction when [Mg2+] o is simultaneously withdrawn from isolated rat aortic smooth muscle. These contractions are Ca2 (+)-dependent and vary in magnitude with the extracellular Na concentration and the Na substitute used. In contrast to substitution with sucrose, mannitol, urea and choline, substitution with Tris or Li+ does not result in contractions, in the absence of [Mg2+] o with these comparatively low [Na+] o reductions. Choline, mannitol, sucrose and urea substitutions sometimes give rise to a fast contractile phase in the presence of [Mg2+] o, which relaxes within a short time (about 5 min). The rises in tension in response to lowering of [Na+] o in the absence of [Mg2+] o are inhibited by the Na+ influx blocker, amiloride. These data are compatible with the hypothesis that Mg2+ controls Na+/Ca2+ exchange in these low Na+ substitution experiments and also protects the cell from osmotically induced small changes in cell volume in rat aortic smooth muscle.