Isosmotic substitution of KCl for NaCl in the physiological solution produces a transient contraction while KCl added hyperosmotically to the physiological solution produces a sustained contraction in guinea-pig taenia coli. Wet weight of the tissue increased in the high K, Na deficient solution. Hyperosmotically added sucrose completely prevented the increase in wet weight although the inhibition of sustained contraction was only partly (approximately 25%) recovered. Hyperosmotic application of NaCl was more effective in maintaining the contraction. When pyruvate or oxalacetate substituted for glucose in the high K, Na deficient solution, the tonic contraction was well maintained. An inhibitor of glucose uptake, phlorizin, did not affect the pyruvate-supported tonic contraction in high K, Na deficient solution although the agent inhibited the tonic contraction induced by high K solution containing Na and glucose. These data suggest that the sustained contraction produced by high K, Na deficient solution is inhibited mainly by an inhibition of utilization of glucose resulting from Na deficiency and partly by a swelling of the smooth muscle in guinea-pig taenia coli.