Objective: To investigate the role of skin biopsy in nitrofurantoin peripheral neuropathy. Design: We describe the clinical features and skin biopsies of 2 cases of non-length-dependent small-fiber neuropathy/ ganglionopathy attributable to nitrofurantoin. Setting: Clinical evaluation and skin biopsies were performed at a tertiary teaching hospital in Baltimore, Maryland. Patients: A 59-year-old woman with disabling generalized dysesthesia and a 53-year-old woman with progressive burning pain in the perineum and extremities. Main Outcome Measures: Slow or incomplete recovery and possibly irreversible damage. Results: The neuropathy was neither dose dependent nor associated with impaired renal function. Results from nerve conduction studies were normal. Skin biopsies revealed distinctive morphologic changes with clustered terminal nerve swellings without evidence of nerve fiber degeneration. Conclusions: These distinct morphologic changes associated with nitrofurantoin have not been previously reported to our knowledge. Skin biopsy appears to be helpful in confirming the diagnosis in these patients.