The goal of this retrospective cohort study was to test the hypothesis that the cramp-fasciculation syndrome (CFS) represents a disorder of peripheral nerve hyperexcitability and to evaluate the accuracy of repetitive nerve stimulation (RNS) for its diagnosis. A consecutive series of 108 patients were evaluated with posterior tibial RNS at 1, 2, and 5 HZ. Abnormal peripheral nerve excitability was defined by the presence of afterdischarges, cramp potentials, or continuous motor unit activity. RNS demonstrated abnormal nerve hyperexcitability in 29 of 36 subjects (81%) with CFS, defined operationally by the presence of both muscle cramps and fasciculations. Based on receiver operating characteristic (ROC) curve analysis, tibial RNS correctly classified the presence or absence of CFS in 75% of subjects. These results suggest that CFS represents a form of peripheral nerve hyperexcitability and, furthermore, that RNS is a clinically useful test for CFS.