In the last few years, substantial evidence has been provided on peripheral nervous involvement in infection by hepatitis C virus (HCV), whilst central nervous involvement is rare. Here, we report a case of acute transverse myelitis in a woman developing 4 years after documented HCV seropositivity, associated with intrathecal anti-HCV protein IgG. Isoelectrofocusing of all CSF samples before and after immunoabsorption with recombinant structural HCV proteins revealed disappearance or marked decrease of some oligoclonal IgG bands suggesting binding to HCV proteins. To our knowledge, this is the first report of acute myelitis associated with intrathecal immune response against HCV proteins. This finding suggests that in acute myelitis of unknown aetiology, testing CSF for HCV RNA and related antibodies is warranted.