Halothane in concentrations used clinically produces contracture in isolated frog sartorius muscle previously treated with caffeine, 0.5 to 1 mM. Contracture produced by caffeine in muscles previously exposed to halothane can be prevented by procainamide but is increased by lidocaine. Similarly, contracture produced by halothane in muscles pretreated with caffeine can be increased by lidocaine, but not by procainamide. However, procainamide added after development of contracture will not produce relaxation. The underlying abnormality in anesthetic malignant hyperpyrexia may be a deficit in the ability of sarcoplasmic reticulum to reaccumulate calcium, allowing a sustained active state of contracture, a situation which can be pharmacologically mimicked by the use of caffeine. If so, it may be that in treatment of malignant hyperpyrexia in man, procainamide rather than lidocaine may be the better drug for attempting alleviation of the abnormal contracture and hypermetabolic state.