Peripheral neuropathy can arise from various mechanisms during hepatitis C virus (HCV) infection, mainly involving associated mixed cryoglobulinemia. The frequency of demyelinating polyneuropathy is probably underestimated in these patients. We report two cases of demyelinating polyneuropathy in HCV-infected patients. The first case concerned a 76-year-old woman followed for hepatitis C associated with a mixed cryoglobulinemia (type II), who developed a chronic progressive distal motor weakness and sensory disturbances concomitant with a raise in serum aspartate aminotransferase (GOT/AST) and alanine aminotransferase (GPT/ALT) levels. Other laboratory studies were normal except for a decrease in the hemolytic fraction of complement to 75 IU (n = 400-520). The second case was a 68-year-old woman followed for hepatitis C associated with a mixed cryoglobulinemia (type II), who had sensory disturbances in the lower limbs. Laboratory studies were otherwise unremarkable. Cerebrospinal fluid studies showed a normal protein content without pleocytosis in both patients. In both cases nerve conduction studies were suggestive of a mixed axonal and demyelinating sensorimotor neuropathy. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation in both cases. The two patients subsequently improved, the first with an antiviral treatment and the second with oral steroids.