Malignant hyperpyrexia is a dangerous complication of general anesthesia occurring in individuals with an underlying disease of muscle. The essential clinical features of the syndrome are a drastic and sustained rise in body temperature, metabolic acidosis, and widespread muscular rigidity. The results of experiments on susceptible pigs and in vitro studies of human muscle have shown that all the clinical features of the syndrome can be explained by a raised level of calcium ions in the myoplasm. This is caused by a massive and sudden release of calcium into the myoplasm from the calcium-storing membranes in the muscle cell when exposed to general anesthetic agents. Two myopathies predisposing to malignant hyperpyrexia have been identified. One is usually subclinical, dominantly inherited, and manifested only by raised serum CPK levels. The other occurs in young boys with a number of physical abnormalities, whose relatives are unaffected. The serum CPK is a useful screening test in families in which malignant hyperpyrexia has occurred. Unfortunately, though, the serum CPK is not a specific test, and in doubtful cases the only unequivocal method of establishing susceptibility to malignant hyperpyrexia is to carry out an in vitro muscle test in which the muscle is exposed to caffeine, halothane, succinylcholine, and potassium chloride. Susceptible individuals should be given local, regional, or spinal anesthesia if an operation is needed. If this form of anesthesia is unsuitable, barbiturates such as thiopentone, tranquilizers such as diazepam, narcotics such as Pantopon, and neuroanaleptics such as fentanyl, nitrous oxide, d-tubocurarine, and althesin appear to be safe. By far the most important aspect of treatment is prophylaxis. Early diagnosis and immediate cessation of the offending anesthetic agents are the most important factors in trying to reduce the very high mortality of the syndrome.