Motor unit counting, a neurophysiologic test, compares the sizes of the potentials of single motor units evoked by weak graded neural stimulation with the response of the whole muscle to a maximal neural stimulus. This test was performed on individuals belonging to families afflicted with malignant hyperthermia (MH) and 2 individuals unrelated to malignant-hyperthermia-susceptible (MHS) patients. The MH status of the patients was confirmed by the skeletal-muscle caffeine contracture test. Two or more of the following muscles or muscle groups were examined in each subject: extensor digitorum brevis, hypothenar muscle groups, the thenar muscles supplied by the median nerve and the soleus. Coaxial needle electromyography was carried out on the brachial biceps or the abductor pollicis brevis, and the vastus medialis or the extensor digitorum brevis. Motor unit counts were lower than the cut-off values corresponding to the selected probability levels in a high proportion of MHS subjects. The proportion was larger in tests utilizing pairs of muscles than in those involving the appropriate muscle types alone. A further increased proportion, and thereby more sensitive discrimination, was obtained by a triple combination of muscles. Concentric needle myopathy (EMG) was not as accurate a prognosticator of the MH trait as was motor unit counting. Motor unit counting confirms that the primary defect of human MH involves motor nerves as well as the skeletal muscle. Motor unit counting also serves as a noninvasive diagnostic test for MH and is only slightly less accurate than the caffeine contracture test.