A simple and specific method for detecting herpes simplex virus infection in routinely processed paraffin-embedded biopsy specimens is described. DNA is extracted from paraffin blocks, and subjected to DNA amplification with the polymerase chain reaction. After 40 rounds, an amplified band can be detected after agarose gel electrophoresis and ethidium bromide staining. This band is specific for herpes simplex virus, because tissues infected with related viruses do not give this amplified band. We have been able to detect viral DNA in small punch skin biopsies with this procedure, which can take as little as 6 h.