Infections with herpes simplex virus (HSV) types 1 and 2 are widespread in all human populations and result in persistent and latent infections. HSV-1 is commonly responsible for orofacial, HSV-2 more likely causes genital lesions. Herpes genitalis is one of the most important sexually transmitted diseases; furthermore, there are severe diseases associated with HSV (e.g., encephalitis). Over the last years an increase in clinical manifestations of HSV has been reported, and HSV-1 has been increasingly discussed as causative agent of herpes genitalis. We retrospectively evaluated the laboratory results of our routine diagnostic service for HSV infections, looking for changes of HSV epidemiology in recent years. Specimens from 2,678 herpes patients were obtained between 1 January 1996 and 31 March 2002. Using cell culture, the presence of HSV was investigated in swabs taken from different body sites, and clinical data on HSV localization and type were evaluated. We found 345 patients positive for HSV-1 and 212 positive for HSV-2. Clinical data were available from 72.1% of the patients with HSV-1, and 61.3% of those with HSV-2 infection. In genital herpes HSV-1 was the causative agent in 20% of men and in 25% of women. In patients suffering from orofacial herpes HSV-2 was detected in 7% of men and in 4% of women. To evaluate the frequency of neurological HSV diseases, 2,406 cerebrospinal fluid samples (CSF) from 2,121 patients suspected of meningitis or encephalitis were tested for HSV DNA by the polymerase chain reaction. Among those patients, 120 showed CSF positive for HSV DNA. Serum surveys of HSV-1 and HSV-2 infection recently established in our region were compared to similar studies performed in Germany 25 years ago. We found that seroprevalences have not changed over the last 25 years and that neurological HSV diseases are rare. However, as in the USA, a significant percentage of herpes genitalis is caused by HSV-1 in Germany.