Salicylate (1-5 mM) had no effect on the peak amplitude (Pt) of twitches elicited at 0.05 to 0.05 Hz, but depressed the Pt in frog and toad "toe" muscles stimulated at 5 to 10 Hz. The maximal tetanic tension (Po) was not reduced significantly by salicylate, but the time to reach Po was increased to several seconds. K-induced contractures were reduced by ca 40 and 50%, respectively, in the presence of 5 and 10 mM salicylate. Pretreatment with salicylate (5 mM) reduced the twitch potentiation by quinine, shortened the duration of twitches in caffeine-treated muscles and inhibited the caffeine- and the quinine-induced contractures. Muscles in contracture because of a previous exposure to quinine relaxed promptly upon addition of salicylate to the bathing medium. The inhibitory effects of salicylate on Pt, on Po and on K- or drug-induced contractures were reversible and were not affected by changes in pH between 7.5 and 6.5. Salicylate depressed the caffeine-rapid cooling contractures (RCC). In toad muscles, this effect was affected markedly by the order in which caffeine and salicylate were applied. Blockade of the caffeine-RCC by salicylate was enhanced by lowering the pH of the medium. Salicylamide (1-5 mM) reproduced the effects of salicylate on the caffeine- and the quinine-induced contractures and the caffeine-RCC. In addition, salicylamide reduced the twitch tension. It is proposed that salicylate and salicylamide affect Casequestration by the sarcoplasmic reticulum.