It has been suspected that the cause of malignant hyperthermia (MH) is an abnormality in the sarcoplasmic reticulum of skeletal muscle. We isolated the sarcoplasmic reticulum from malignant hyperthermia-susceptible (MHS) patients and controls and analysed the protein composition with sodium dodecyl sulfate polyacrylamide gel electrophoresis. There were no remarkable changes in the sarcoplasmic reticulum protein composition profile of the scanned gel of the patients. Quantitative measurement of the relative proportion of each band in the gel, however, revealed a slight decrease in calsequestrin and a slight increase in protein of molecular weight 23,000. (Ca2+ -Mg2+)ATPase had no altered subfragments in MHS patients. Crude mitochondrial proteins and myoplasmic proteins showed minor alterations in composition in some patients. The data supported the thesis that malignant hyperthermia is due to defects in several different cell membranes including the sarcoplasmic reticulum and the mitochondria.