A population of individuals with a high incidence of genital herpes simplex virus type 1 (HSV-1), due most likely to oro-genital contact, was examined to determine the incidence of oral herpes simplex virus type 2 (HSV-2) infection. Herpes simplex virus was isolated from the oral cavity of 43 college students whose symptoms ranged from singular lesions of the lips with minimal discomfort to severe oral disease with systemic involvement resulting in lymphadenopathy, chills, sweat, myalgia, and fever. The virus isolated from each case was identified by serum neutralization and typed as HSV-1 or HSV-2 using (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) sensitivity, monoclonal antibody immunofluorescence, and restriction endonuclease EcoRI digestion of viral DNA. In every instance the isolate was HSV-1. Additional identification and typing of head and neck isolates as well as oral samples from non-university patients demonstrated that all were also HSV-1. Therefore, while HSV-1 appears to be readily transmitted to the genitalia in this group of individuals, the transmission of HSV-2 to the oral cavity may not be as common, even though clinical histories revealed that several of these patients were engaging in oro-genital contact.