Histopathologically, the skin lesions of acute herpes zoster (AHZ) are characterized by epidermal necrotic vesicles with inflammation. Nitric oxide (NO) is generated from L-arginine by nitric oxide synthase (NOS), and immune inflammation involves the activation of NOS in both effector cells and target cells. NO can cause apoptosis and necrosis of target cells such as keratinocytes. We proposed that a large burst of NO in AHZ may cause the epidermal necrosis. Skin biopsies were taken from 13 patients with AHZ. The expression of inducible-type NOS (iNOS) was examined by immunoperoxidase staining and reverse transcription-polymerase chain reaction (RT-PCR). In the skin specimen of AHZ, moderate-to-strong staining for iNOS was observed in inflammatory cells and necrotic keratinocytes, while weak staining was observed in non-necrotic peripheral keratinocytes. RT-PCR using skin specimen of AHZ corroborated the immunoperoxidase findings, yielding bright bands for iNOS. Normal control skin showed minimal or negative expression both by immunoperoxidase stains and RT-PCR. Increased expression of iNOS is consistent with the hypothesis that high level of NO induced by iNOS may be associated with the epidermal necrosis with inflammation seen in the skin lesions of AHZ.