Human serum having complement fixation anti-herpex simplex virus activity was reacted with herpes simplex virus infected cells in tissue culture. By tagging the antibody to ferritin and examining the cells in the electron microscope, it was found that 1. the entire surface of the infected cell is antigenically altered and reacts with hyperimmune serum. The antigenic cell surface change is not limited to structurally altered sites, nor is it limited to sites where virus particles are present, and 2. cells in the early stages of infection react more strongly with hyperimmune serum than do cells in later stages. The possible clinical significance of the infected cell surface - antibody reaction is discussed.