Abstract-The effects of ouabain on contraction, cellular Na concentration, and 45Ca uptake of various smooth muscle tissues depolarized by high-K (62.7 mM) solution were studied.In the taenia coil and ileum isolated from guinea-pig, ouabain (2x10-6 M 5x10-5 M) increased cellular Na con centration and strongly inhibited K-contraction. A good correlation between cellular Na concentration and inhibition of tension was obtained both in the taenia coil and ileum. In the portal vein, aorta, and uterus, ouabain failed to induce relaxation and slightly increased the cellular Na. A long-time exposure to ouabain (1 X 10-3 M) attenuated the response to high-K in the portal vein and uterus but not in the aorta. The inhibitory effect of ouabain in the taenia coil and ileum was antagonized by an increase in external Ca, and the inhibition was accompanied by a decrease in cellular 45Ca content . A possibility exists that excess cellular Na inhibits K-induced Ca influx, although there is a tissue-specific difference.The data also suggest that the inhibitory effect of Na-accumulation is dissimilar to that of verapamil with respect to the tissue-specific difference.