Most of the current antiherpetics target viral DNA polymerase, but with the emergence of drug-resistant viruses, antiherpetics with different targets have become necessary. Inhibition of herpes simplex virus (HSV) replication at the early stages of infection minimizes cytotoxicity and immune suppression induced by HSV infection. In this report, quantitative reporter systems that use recombinant HSV and a stably transfected cell line were developed for the screening of agents targeting the early stages of HSV infection. The reporter genes in both systems were directed by HSV immediate-early (IE) promoters, so considerably less time was required for the quantification of HSV infection than the traditional plaque reduction assay. The results show that both reporter assays were sensitive to antiherpetic screening. Both assays were quantitative, rapid, easy to perform, and highly adaptable for automatic high-throughput screening. Exploiting the flexibility of these 2 assays, modified assays were also proposed for the detailed analysis of antiherpetic mechanisms.