To examine the sensitivity of human oral mucosa to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection, human gingival mucosa explants were infected with either HSV-1 or HSV-2 in vitro and the expression of virus specific antigen was examined by the immunofluorescent antibody technique. HSV-2 antigen was found in the basement membrane, basal cell layer and lower prickle cell layer. This finding was consistent with the HSV-1 infection. Electron microscopic study revealed the presence of nucleocapsids and enveloped virus particles in the basal cells of HSV-2-infected organ cultures. These findings indicate that human gingival mucosa is sensitive to infection with HSV-2, as well as HSV-1, and that the virus may replicate in the undifferentiated epithelial cells of mucosal epithelium.