We report a case in which a man presented with a papulovesicular rash with centrifugal distribution ( Figure 1 ) that had been preceded by four days of headache, backache, fever, nausea, and vomiting. Because the rash started on the face, evolved slowly, and was in the same stage of development on any one part of the body, smallpox was considered in the differential diagnosis. Urgent consultation was obtained, and health departments and the Centers for Disease Control and Prevention (CDC) were contacted. Limited specimens sent to the hospital laboratory tested positive for varicella–zoster virus (VZV) IgG, negative for VZV on direct fluorescent-antibody staining, and negative for the human immunodeficiency virus on serologic analysis. Digital photographs were e-mailed to the CDC. Specimens were collected according to CDC guidelines1 and sent to the CDC. A culture performed at the CDC was positive for herpes simplex virus (HSV) type 2.