An indirect immunofluorescence method, based on the use of infected Hela cell coverslip cultures was developed to demonstrate human IgM and IgG class antibodies against herpes simplex virus (HSV) type 1 induced cell surface antigens. A total of 35 specimens from 20 patients have been tested; including patients with a clinical diagnosis of HSV type 1 or type 2 primary infection, patients with recurrent HSV infections, patients without any HSV infections, and patients with varicella-zoster virus (VZV) infections. In each patient with a primary HSV infection both IgM and IgG antibody response was observed, while the patients with recurrent HSV infections showed only IgG antibodies. The direct serological typing of HSV infections was not possible because of cross-reacting antibodies both in the IgG and IgM test. No cross-reactivity was found in this test with HSV and VZV antibodies. The HSV fluorescent IgG and IgM antibody titers were found to parallel the highly sensitive HSV radioimmunoassay antibody titers very closely though at a markedly lower level.