Malignant hyperthermia susceptibility is genetically heterogeneous. The ryanodine receptor gene on the long arm of chromosome 19 represents an important candidate gene but not all families with malignant hyperthermia demonstrate ryanodine receptor mutations or linkage to this region of 19q. Linkage to chromosome 17 in the region of the adult muscle sodium channel alpha subunit gene has been suggested in some families; others are not linked to either of these loci. For most families the in vitro muscle contracture test remains the only reliable method of predicting susceptibility to malignant hyperthermia. We have performed linkage analysis in a large family group with malignant hyperthermia in which the in vitro muscle contracture test had been carried out using the procedure standardised by the European Malignant Hyperthermia Group. None of the published ryanodine receptor gene mutations associated with malignant hyperthermia susceptibility were detected in affected individuals but linkage to intragenic ryanodine receptor markers strongly suggest that this gene is involved in malignant hyperthermia susceptibility in this family. This enabled accurate predictive testing by DNA analysis in 11 untested subjects at 50% risk.