We report a case of mononeuropathy multiplex due to interferon alpha (IFN alpha) therapy for chronic hepatitis C. A 61-year-old man received IFN alpha (natural type 6 x 10(6) IU), every day for two weeks and three times a week for 22 weeks by intramuscular injection. Seventeen weeks after the initiation of IFN alpha therapy, he noticed painful dysesthesia, muscle weakness and muscular atrophy of the left lower extremity. Neurological examination revealed weakness of the left iliopsoas, quadriceps femoris and femoral adductor muscles, hypesthesia and dysesthesia. Electromyogram showed neuropathic change in the left vastus lateralis muscle. Muscle computed tomography showed muscular atrophy of the left lower extremity. Two months after discontinuation of the IFN alpha therapy, dysesthesia and muscle weakness of the left lower extremity improved spontaneously. He was diagnosed as mononeuropathy multiplex of the left femoral nerve and obturator nerve caused by IFN alpha therapy. Attention must be paid to dysesthesia, muscle weakness and muscular atrophy when IFN alpha therapy is initiated.