The performance of a human herpesvirus 8 (HHV-8) enzyme immunoassay (EIA) and selective subsequent use of an HHV-8 immunofluorescence assay (IFA) was tested in persons unlikely to be infected with HHV-8 and those who had HHV-8 detected in their saliva. The IFA was performed on samples within a range of EIA optical densities (0.15 to 0.35) where there was considerable overlap between HHV-8-infected and uninfected individuals. The sensitivity of the testing strategy was 88%, with a specificity of 97%.