The attachment of streptococci and staphylococci to cells infected with influenza virus has been previously reported and has been correlated with the increased incidence of these bacterial infections during flu epidemics. The present work was initiated to determine whether infection with herpes simplex virus (HSV) might lead to preferential bacterial attachment. HEp-2 cells were grown in monolayer and infected with HSV, Type I or Type II. Twenty-four hours later the cells were incubated with suspensions of various organisms, including Group A and B streptococci, Staphylococcus aureus, Propionibacterium acnes, and Candida albicans. After incubation for one hour, the cells were washed and fixed. Bacterial adherence and virus infection were assessed by scanning electron microscopy (SEM) as well as conventional light and transmission electron microscopy (TEM). Only Group A streptococci adhered to virus-infected cells, both to cells infected with HSV, Type I and those infected with HSV, Type II. SEM and TEM revealed bacteria attaching to cells with budding virus particles. Preincubation of infected cells with anti-HSV serum prevented bacterial adherence. These findings suggest that infection of oral epithelium with HSV might lead to superinfection with Group A streptococci.