Herpes simplex virus (HSV) infections causing severe disease are reported frequently in patients suffering from human immunodeficiency virus (HIV) infection. This disease pattern may also be seen in an immunocompromised disease state with other causes, however, as in the case presented in this paper. An 84-year-old woman had hepatic cirrhosis resulting from chronic hepatitis C virus infection. The woman developed ulcerative lesions in and around her mouth and in the genito-anal region, and these persisted for some months. Diagnosis of HSV infection was not obtained until after extensive laboratory investigations. Aciclovir infusion therapy started immediately afterwards led to dramatic improvement of the skin and mucous membrane changes. Complete clearing of lesions was not obtained, however, because the patient died as a result of the immunosuppression.