Buciclovir is an acyclic guanosine analog with activity against herpes simplex virus (HSV). Buciclovir is phosphorylated to its triphosphate form by HSV thymidine kinase in infected cells and acts as a specific inhibitor of the viral DNA polymerase. Buciclovir inhibited DNA synthesis, not RNA synthesis, and prevented an increase in the size of newly synthesized DNA. Topical treatment initiated early after infection was efficacious, in contrast to topical treatment delayed 24 h or more. Systemic treatment of infected mice could not prevent the spread of the virus to the brain and mortality. Systemically administered buciclovir had an effect in guinea pigs, even after the delayed onset of treatment, but this effect required high doses of the drug. Buciclovir has only a limited effect against herpesvirus infections once the virus is present in the nervous systems of infected