Histologic studies of Charcot-Marie-Tooth disease, type I, show a contrast between the lesions of myelinated fibers and the normality of unmyelinated fibers. Conventional electrophysiologic tests only demonstrate the alteration of myelinated fibers but do not study unmyelinated fiber function. We present routine clinical tests that are easily available and effective for the evaluation of small unmyelinated fibers: thermal threshold testing for warmth to evaluate small C unmyelinated somatic fibers and sympathetic skin responses to evaluate small C unmyelinated sympathetic fibers. Five unrelated patients with a diagnosis of Charcot-Marie-Tooth disease, type I, confirmed by biopsy were investigated. All of these patients showed marked reduction or absence of motor and sensory conduction velocities and severe denervation at needle examination. By contrast, thermal threshold testing for warmth and sympathetic skin responses were normal, confirming the normality of small C unmyelinated somatic and sympathetic fibers. We conclude that these noninvasive tests are helpful in the diagnosis of Charcot-Marie-Tooth disease, type I.