Recrudescent herpes labialis (RHL) is a disease caused by herpes simplex virus (HSV), predominantly type 1 (HSV-1). We have monitored HSV-1 shedding in the oral cavity by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays (ELISA) using digoxigenin-labeled primers designed to amplify a 278 bp segment of the HSV-1 UL 42 region. Prodromal RHL was confirmed by thermographic imaging in 22 patients. Infectious virus was not detected using tissue culture for virus isolation (0/22). Using PCR and agarose gel electrophoresis, we could detect HSV-1 DNA in 8/22 patients. Using a biotinylated-probe internal to the predicted sequence of the PCR product, HSV-1 DNA was detected in 10/22 patients by ELISA. We conclude that HSV-1 DNA is shed into the oral cavity of patients presenting with sub-clinical RHL and that the PCR-ELISA technique represents a more sensitive method to monitor HSV-1 shedding than conventional tissue culturing or PCR-electrophoresis alone.