In earlier work on malignant hyperthermia (MH) susceptible pigs the concentration of muscle metabolites differed from that found in normal control pigs. Therefore, in the present study these metabolites were measured in human muscle biopsies to find out whether normal individuals could be discriminated from MH-susceptible persons. Analysis of skeletal muscle metabolites was performed on skeletal muscle obtained from humans (n = 68) being screened to exclude or confirm susceptibility to MH. Three groups were identified based on the reaction pattern of a skeletal muscle sample exposed in vitro to caffeine or halothane 1% plus caffeine: 1) MH susceptible (MHS; n — 19); 2) normal humans, (controls; n = 31); and 3) intermediatereaction type (K-type: n = 18). No significant differences were found in metabolite levels of phospbocreatine (normal, MHS, and K-type: 13.20 vs. 13.74 vs. 14.42 nmol/mg wet weight, respectively), creatine (16.30vs. 16.94vs. 15.06 nmol/mg wet weight, respectively), adenosine triphospate (3.75 vs. 3.98 vs. 3.89 nmol/mg wet weight, respectively) and lactate (3.73 vs. 3.65vs. 3.79 nmol/mg wet weight, respectively). It is concluded that analysis of skeletal muscle metabolites cannot be used as a screening test to confirm or exclude MH susceptibility in humans.