Using in vivo 31P NMR spectroscopy, the authors compared the NMR spectra of the flexor muscles of the forearm from 13 humans characterized as MH susceptible on the basis of in vitro caffeine/halothane contracture tests with those from 25 normal controls. The levels of phosphocreatine (PCr), inorganic phosphate (Pi), and ATP during rest, graded exercise, and post-exercise recovery were measured in their forearms. MH susceptible subjects had significantly (P less than 0.001) higher Pi/PCr values (0.222 +/- 0.009) at rest than did normal controls (0.140 +/- 0.004). In addition, a significantly (P less than 0.01) slower post-exercise recovery rate was found in the MH-susceptible group. There was no significant difference between the two groups in the relationship of work rate to Pi/PCr. These data suggest that unchallenged MH susceptible patients can be distinguished from normals using 31P NMR spectroscopy. The potential use of this technique as a non-invasive tool in determining MH susceptibility is discussed, as well as the possible mechanisms underlying the observed 31P NMR abnormalities.