Recurrent oral herpes simplex virus lesions are common in both immunocompetent and immunocompromised persons. In contrast, cytomegalovirus-associated intraoral lesions are rarely seen, even in the immunocompromised host. We report a case of concurrent oral herpes simplex virus and cytomegalovirus infection, appearing as an ulcerative lesion of the labial mucosa in a patient with acquired immunodeficiency syndrome. Herpes simplex virus type 1 was shown to be present in the lesion by culture tests, histopathologic examination, immunohistochemistry findings and a direct immunofluorescence assay, and cytomegalovirus by histopathologic examination and immunohistochemistry findings. We deduce that the lesion was due to concurrent herpes simplex virus-1 and cytomegalovirus infection. The patient responded well to 2 weeks of treatment with a high dose of acyclovir.