Xenon has many characteristics of an ideal anaesthetic agent. It is not known whether xenon is a safe alternative to the potent inhalational anaesthetics in patients susceptible to malignant hyperthermia (MH). We investigated the effect of xenon, halothane and caffeine on muscle specimens of 31 individuals, referred to the MH Unit of the University of Ulm, and performed genetic epidemiology. Thirteen individuals were classified as MH susceptible and 18 as MH negative. Xenon 70% did not cause an increase in baseline tension of any MH-susceptible muscle specimen in contrast to halothane and caffeine. The evoked twitch response increased transiently in MH-susceptible and normal specimens indicating a mechanism independent of MH susceptibility. These results suggest that xenon, in concentrations up to 70% may be a safe anaesthetic for MH-susceptible patients.