Background We have previously reported that low humidity amplifies the hyperproliferative and inflammatory response to barrier disruption. Other reports suggest that epidermal interleukin (IL)-1 alpha is stimulated by various factors related to epidermal inflammation and that it may induce other proinflammatory molecules, Objectives To evaluate the generation of IL-1 alpha in the skin of hairless mice kept under various conditions of environmental humidity, Methods We carried out an immunohistochemical study, and evaluated epidermal IL-1 alpha mRNA and protein levels, and release of IL-1 alpha from skin after tape stripping, in hairless mice kept under low or high humidity. Results The immunohistochemical study showed that the amount of IL-1 alpha in the epidermis was higher in animals kept in a low-humidity environment than in a high-humidity one, The epidermal IL-1 alpha mRNA and protein levels increased significantly when the animals were kept under low humidity, Moreover, the release of IL-1 alpha from skin immediately after tape stripping was significantly higher in animals kept in a low-humidity environment than in a high-humidity one. Conclusions These results suggest that IL-1 alpha is an important factor in mediating the relationship between environmental humidity and epidermal pathology.