The complex immunological effects of interferon and ribavirin therapy (IFN/R) in hepatitis C virus (HCV) may also exacerbate or trigger the de novo development of autoimmunity. We report the first case of IFN/R therapy associated with Vogt-Koyanagi-Harada disease, a T-cell-mediated autoimmune response to melanocytes. This condition, which has characteristic ocular, neurological and integumentary findings, elicits a systemic prodrome that may mimic side-effect profile and delay of IFN or mask its recognition. We discuss this disease in the context of the known immunomodulatory effects of IFN-alpha and ribavirin and suggest potential mechanistic explanations for the association.