Inherited susceptibility to malignant hyperthermia has been recognized in Poland China swine. Clinical and laboratory studies were made to compare the syndrome with that observed in man and in other breeds of swine in South Africa and Europe. Malignant-hyperthermia-susceptible (MHS) swine were identified by increased ATP depletion in biopsied muscle studiedin vitro. MHS and related swine had elevated serum creatine phosphokinase values compared with control swine (MHS swine &OV0335; 2,435 IU/l; MHS-related swine &OV0335; 1,260 ID/l; control swine &OV0335; 144 IU/l). The syndrome was triggered by administration of halothane and of succinylcholine chloride. Resulting clinical responses, in order of appearance, were tachycardia, hyperventilation, skeletal muscle rigidity, hyperthermia, cardiac arrhythmias, and death. Blood chemical responses which occurred early in the syndrome included hypercapnia, acidosis, elevated plasma inorganic phosphorus, and lactacidemia. The malignant hyperthermia syndrome in this breed of swine appears similar to that in Land-race and Pietrain swine, and in man. The Poland China swine is an appropriate animal model for the study of this disease.