BACKGROUND The diagnosis of herpes zoster is mostly based on clinical findings. In atypical cases, rapid and reliable virological diagnostics is necessary because effective antiviral chemotherapy is available. METHODS The meaningfulness and practicability of conventional diagnostic methods mostly used such as antigen staining, virus isolation and detection of virus-specific antibodies were compared with polymerase chain reaction (PCR) in 100 patients with zoster. RESULTS PCR using oligonucleotides selected from the open reading frames 28 and 29 of the varicella-zoster virus (VZV) genome showed the highest sensitivity of 94% and a specificity of 100%. Direct immunofluorescent antigen staining carried out within few hours had a sensitivity of 82% and a specificity of 70%. However, results could only be obtained in 71% of the cases. On the basis of serologic parameters, an active VZV infection was detected in 61% of the patients. Virus culture frequently regarded as "gold standard" was successful in 20%. There was a strong dependence on the time of collecting specimens and the immunocompetence of the patients. CONCLUSIONS The study shows that the PCR has to be considered the method of choice for the diagnostics of zoster with an atypical course. Serological methods can only be recommended to confirm the diagnosis retrospectively.