BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated primarily, but not exclusively, with mutations in the skeletal muscle ryanodine receptor. Associated environmental factors, however, may also be important for expression of the syndrome. METHODS AND RESULTS: A 24-yr-old trauma patient developed a fulminant MH crisis after a 3 minute exposure to sevoflurane. A thorough evaluation of underlying co-morbidities revealed a number of environmental factors that could have altered skeletal muscle calcium regulation, and may have potentially influenced the effects of volatile inhaled anesthetics. Since MH is a syndrome characterized by abnormal skeletal muscle calcium regulation, other factors that alter calcium homeostasis may exacerbate the impact of inhaled MH-triggering drugs. CONCLUSIONS: While a thorough history of MH episodes in a proband and family is emphasized as part of a complete preanesthetic evaluation, obtaining a history of other environmental entities that may alter calcium regulation may be equally important to knowing the family history.