Reported is a case of multiple mononeuropathy which appeared during the administration of recombinant interferon-alpha 2a (rIFN-alpha 2a) for treatment of chronic hepatitis C. A 38-year-old man received an intramuscular injection of rIFN-alpha 2a, 6 x 10(6) IU, every one or two days for a nine week period. Seven weeks after the initiation of rIFN-alpha 2a therapy he developed numbness of the tongue and extremities and weakness of the upper extremities. Neurological examination revealed an asymmetrical disturbance of touch and pain sensation in the tongue, trunk, left shoulder and extremities accompanied by painful dysesthesia. Moderate weakness and muscular atrophy were noted in the right hand and left shoulder. Electrophysiological studies showed the amplitude of the compound muscle action potentials and sensory nerve action potentials were significantly decreased, when the right median and ulnar nerves were stimulated. Additionally, the conduction velocities were normal and needle electromyography showed fibrillation potentials suggesting an axonal form of multiple mononeuropathy. Biopsies of the muscle and nerve failed to show pathological changes, however. The clinical and electrophysiological abnormalities reduced gradually with methyl-prednisolone pulse therapy and administration of prednisolone and mizoribine. Therefore, in this case, administration of rIFN-alpha 2a may have induced multiple mononeuropathy of the axonal form.