Fixed drug eruption (FDE) is an uncommon adverse drug reaction caused by delayed cell-mediated hypersensitivity. Acyclovir and its derivatives (valacyclovir, famciclovir) are synthetic purine nucleoside analogues for antiviral medication and there have been few report of FDE related to these antiviral agents. A 51-year old female patient presented with recurrent, dusky, erythematous patches and multiple pigmentations at fixed sites after taking valacyclovir for herpes simplex infection. The patient had already experienced similar adverse reactions after administration of acyclovir . To make a definite diagnosis, patch test and prick test at the sites where eruption occurred were performed. However, the patch and prick tests with acyclovir and its derivatives showed negative response. The open oral challenge test was done with valacyclovir and famciclovir separately, and the well-defined erythema developed within 24 hours after ingestions of the medication respectively. Skin biopsy was performed from patch on thigh, and histopathological findings were consistent with FDE. Our results strongly suggest that this case can be considered as FDE due to acyclovir and its derivatives. Although cutaneous adverse eruptions after administration of antiviral agents like this case are very rare, physicians should consider the potential for FDE due to acyclovir and cross reactions with its derivatives including valacyclovir and famciclovir.