In frog fast skeletal muscle, we find a decline of twitch, tetanus, and maximum K and caffeine contracture tensions as tonicity of the bathing solution is increased. The decline of tension independent of the method of producing contraction indicates that the major effect of hypertonicity is directly on contractile tension probably because of the increased internal ionic strength. However, there is some apparent disruption of excitation-contraction (E-C) coupling in solutions made three times the normal tonicity (3T solutions) since: (a) in ST solutions tetanic and K contracture tensions decline to zero from a value near the average maximum caffeine contracture tension at this tonicity (10 % of 1T tetanic tension). At this time, caffeine contractures of 10 % of 1T tetanic tension can be elicited; (b) once the K contracture tension has declined, elevated [Ca++]°, 19.8 mM, restores K contracture tension to 13 % of IT tetanic tension. This probable disruption is not caused by changes in mechanical threshold since in Zl" solutions the mechanical threshold is shifted by 12 mv in the hyperpolarizing direction. This is consistent with neutralization of fixed negative charges on the inside of the membrane. The repriming curve is also shifted in the hyperpolarizing direction in 2T solutions. Shifts of the repriming curve coupled with membrane depolarizations in 3T solutions (about 20 my) may produce loss of repriming ability at the resting potential and disruption of E-C coupling.It has been known for over 60 years that hypertonic solutions can decrease contractile tensions in skeletal muscles (Overton, 1902;Ernst, 1926) and that cells m a y be excitable under conditions where tension is vanishingly small (Demoor and Philippson, 1909;Ernst, 1926). Hodgkin and Horowicz (1957) stimulated renewed interest in the effects of hypertonic solutions on excitationcontraction (E-C) coupling in skeletal muscle by showing that bathing a muscle fiber in solutions made 2.5 times the normal tonicity of Ringer solution abolished twitch tension while leaving the action potential virtually unaffected. T h e y also found that tetanic tension was about one-third of that at