A 39-year-old man developed sequential acute mononeuropathies involving both median, both ulnar, and the right radial and left peroneal nerves. Electrophysiology demonstrated an asymmetric sensorimotor axonal polyneuropathy; nerve biopsy confirmed a vasculitis. Laboratory evaluation revealed a mixed cryoglobulinemia and active hepatitis C infection. The patient stabilized with prednisone/cyclophosphamide/interferon-alpha. Hepatitis C should be considered in the differential diagnosis of mononeuropathy multiplex. Accurate diagnosis is important, as interferon-alpha may prevent transition to chronic hepatitis/cirrhosis.