The induction of heme oxygenase-1 (HO-1) by ultraviolet A (UVA) (320-400 nm) radiation provides a protective cellular defence against oxidative stress, and has been well demonstrated in cultured human skin fibroblasts, although keratinocytes were unreactive. The UVA responsiveness of HO-1 however, has not been confirmed in intact skin. Previously, we reported that UVA-inducible HO enzyme activity in mouse skin is protective against UVB-induced immunosuppression. This study identifies the induced HO isoform and its localization in mouse skin irradiated in vivo with such an immunoprotective UVA dose. We found that HO-1 mRNA was expressed in UVA-irradiated skin, but not in normal or UVB-irradiated skin, whereas constitutive HO-2 was always present. UVA-irradiated skin had increased HO enzyme activity and bilirubin content, and decreased heme content, consistent with HO-1 induction. In situ hybridization and immunohistochemical staining localized HO-1 mRNA and protein to both epidermis and dermis, with strongest expression in basal keratinocytes and weaker expression in dermal fibroblast-like and other cells, in contrast with UVA-induced HO-1 in cultured human skin fibroblasts. This suggests that cultured skin cells may not fully represent skin functions in vivo, or that there may be inherent differences between human and hairless mouse skin HO-1 responses.