BACKGROUND Primary herpes simplex virus (HSV) infection usually involves one mucosal region. OBJECTIVE To describe an unusual disseminated HSV-1 infection involving two mucosal sites in a healthy man. RESULTS Primary HSV infection involved oral and genital mucosa and was associated with viremia, hepatitis and rash. Phylogenetic analysis of genital and oral viruses revealed that the patient was infected by a single HSV-1 strain. CONCLUSIONS Use of polymerase chain reaction detection techniques for HSV may identify viremic patients in the absence of obvious immunosuppression.