Metabolic, hemodynamic and neuroendocrine responses to the combined use of halothane and succinylcholine (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH). Constant-volume ventilation was used, and no therapy was instituted. The overall response in susceptible swine was fulminant, in that it involved the rapid onset of SCh-induced MH combined with the more severe metabolic, endocrine, and cardiovascular effects of halothane-induced MH. Maximal changes in Vo2were equivalent with cither drug or both combined, while changes in lactate, potassium (K+),pH, and catecholamines were perhaps synergistic. Utilizing similar measurements, procaine or procainamide was used in 20 susceptible swine in attempts to prevent MH initiated by halothane, SCh, or both. Recommended therapeutic doses of either drug did not prevent characteristic MH changes in oxygen consumption, cardiac output, lactate. K+,pH. catecholamines, or temperantre.