Are myotonias and periodic paralyses associated with susceptibility to malignant hyperthermia? Excised muscles from patients with myotonia or periodic paralysis were subjected to the in vitro contracture test for susceptibility to malignant hyperthermia (MH). In a group of 44 patients, this standard test gave four positive, 10 equivocal and 30 negative results. The results for 27 control muscles from normal subjects were negative. When the test was performed with less than normal concentrations of contracture-triggering substances (caffeine less than or equal to 2 mmol litre-1, less than or equal to 2% halothane), 70% of the muscles from the patients and only 15% of the controls responded with small contractures (less than 0.2 g). These results should not be taken to indicate that the patients have the genetic trait for MH. The positive and equivocal test results, in addition to the slight contractures, may be accounted for by the electrical after-activity in the cases of pure myotonia, and by increased resting myoplasmic [Ca2+] in myotonic dystrophy. This shows that the in vitro contracture test lacks specificity. 