Acyclovir-d4 is intended for use as an internal standard for the quantification of acyclovir by GC- or LC-MS. Acyclovir is a guanosine analog that has antiviral activity in vitro against the herpes simplex viruses, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpes virus 6 (ID50s = 0.1-63.1 μM). It diffuses freely into cells and is selectively converted into acyclo-guanosine monophosphate by a virus-specific thymidine kinase. During DNA replication, the phosphorylated form of acyclovir is preferentially incorporated into viral DNA, resulting in premature chain termination and inhibition of further DNA polymerase activity. Acyclovir (5 mg/kg) reduces viral titers in mice infected with the herpes simplex virus-1 (HSV-1) strain SC16.