To evaluate usefulness of Ag+ contracture as a tool for elucidating the mechanism underlying the excitation-contraction coupling, the effects of tetracaine on Ag + contracture were compared with those on K + and caffeine contractures in frog skeletal muscle. Tetracaine less than 100 /1M shortened the duration of 120 mM K+ contracture, without affecting tension amplitude. At higher concentrations of tetracaine, K + contracture was inhibited dose-dependently and the duration shortened. Treatment of the fibers with 20-500,uM tetracaine for 3 min did not block the contracture induced by 25 mM caffeine. Effects of tetracaine on Ag+ contracture were similar to those on K + contracture. In the presence of 200 µM• tetracaine, 41 % inhibition was observed in 120 mM K + contracture, while 43% in 100 ,uM Ag + contracture. Also, 200 ,uM tetracaine completely inhibited the contractures induced by 40 mM K+ or 5 JiM Ag+. These findings suggest that the Ag + may induce contractures via its action on the T/SR junction, not a direct action on the SR. Therefore, understanding the mechanism involved in the development of Ag+ contracture would be helpful to elucidate the mechanism of excitation-contraction coupling.