Introduction: An elevated level of plasma homocysteine (eHcy) is a recognized risk factor for many neurological conditions. Recent laboratory studies show a toxic effect of homocysteine causing neuropathy. Clinical observations disclosed that eHcy exacerbates prevalence and severity of peripheral neuropathy in diabetic patients. We have seen a group of neuropathy patients with an eHcy without any other identifiable etiology. We termed this entity as isolated eHcy-induced neuropathy (IHIN) and studied the electrophysiologic features of IHIN. Methods: Conventional nerve conduction study and needle electromyography were performed in the upper and lower extremities of IHIN patients. Results: Twenty-six arms and 26 legs of 28 cases of IHIN were studied. The electrophysiologic studies showed that 93% (26/28) of the IHIN patients had electrodiagnostic abnormalities including 75% (21/28) having mild sensorimotor neuropathy, 18% (5/28) with the electrophysiologic features of carpal tunnel syndrome; while only 7% (2/28) normal findings. Conclusion: Our results suggested that IHIN is a large fiber neuropathy with electrophysiologic features of demyelination and axonal denervation.