Genital herpes is the leading viral sexually transmitted disease in Japan and its treatment is a great matter of concern. From the pathogenetical viewpoint, there are two types of infection, namely the primary and the recurrent or provoked type, the latter being caused by reactivation of latently infected herpes simplex virus (HSV). In women, 41.5%% of genital herpes has been caused by HSV-1 and the remaining 58.5% by HSV-2. Fifty eight per cent of the acute type, mainly primary infection, was caused by HSV-1 and 42.0% by HSV-2. The recurrence rate within one year after primary infection was 86%% for HSV-2 and 25 for HSV-1 patients. On the other hand 84.3%% of the recurrent type and 87.8% of the provoked type were caused by HSV-2. Although three nucleoside analogs (Acyclovir, Valacylovir, Famciclovir) have been developed for treatment of herpes virus infection, and are currentoly being used in the USA and UK, only acyclovir (ACV) is available for the systemic treatment of genital herpes in Japan. The regimen permitted by social insurance for the treatment of genital herpes is ACV 200 mg orally five times a day for five days. The duration of administration is shorter than that being used in the USA (7-14 days) and seems to be too short because in several patients the HSV culture is still positive after 5 days of administration of ACV. To prevent recurrence, suppressive therapy using ACV has been introduced but has not yet been approved by social insurance. Biological response modifiers such as PS-K (a protein-bound polysaccharide) or Lactoferrin are being tried to reduce the recurrence rate. The susceptibility of HSV strains to ACV which had been isolated in 1970 s, 1980s, and 1990 s was examined by a plaque assay which elucidated an almost similar susceptibility among these isolates.