Infection with hepatitis C virus (HCV) can be associated with demyelinating polyneuropathy that may be responsive to immunomodulatory therapy. In this case report series, we review four patients (all male, ages 47-60 years) with HCV and demyelinating polyneuropathy. Two of the four patients were diagnosed with HCV during the course of initial neuropathy evaluation. All patients had sensory loss, absent/diminished reflexes, lower extremity weakness (except for one patient), and demyelinating electrodiagnostic features. Three patients had polyclonal hypergammaglobulinemia and one patient had IgM monoclonal gammopathy. Intravenous immunoglobulin resulted in improvement in three patients; one patient had no benefit from rituximab therapy, but his symptoms have been stable. Demyelinating neuropathy may develop in patients with HCV unrelated to antiviral therapy. Immunomodulatory therapy may be beneficial in some cases. Testing for HCV should be considered, especially in patients with hypergammaglobulinemia or IgM monoclonal gammopathy.