A 66-year-old man was treated for chronic active hepatitis C with 3 MU of recombinant interferon alfa-2a three times weekly. Nine months before interferon therapy, a mild lichen planus had been diagnosed, which exacerbated within 4 weeks of treatment to a generalized erosive lichen planus. After 8 weeks, interferon therapy was stopped because local measures did not improve skin lesions. Otherwise, the patient tolerated interferon therapy well, and the initially 20-fold elevated aminotransferase levels returned to normal. Four weeks after discontinuation of interferon therapy, nearly all mucosal and skin lesions had disappeared. But 8 weeks after the discontinuation, aminotransferase levels again rose to 10 times the normal range. Treating physicians should know that a preexisting lichen planus will potentially exacerbate as a side effect of interferon alfa-2a therapy of a chronic hepatitis. However, because this is the first report on this association, further observations are needed to decide the clinical relevance.