Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are 3 cytokines that play a key rôle in cutaneous homeostasis and in the immunopathogenesis of a number of dermatologic diseases. Most studies have focused on their production by keratinocytes and Langerhans cells. To determine whether there are non-epidermal sites of cytokine transcription, biopsy specimens of normal human skin were probed for IL-1 alpha, IL-1 beta and TNF-alpha messenger RNAs using the method of in situ hybridization. The results demonstrate that each cytokine mRNA is present at multiple sites within the skin, including epidermal appendages and adnexal structures (hair follicles, sebaceous glands), the dermal microvasculature, arrectores pilorum smooth muscle, and the dermal connective tissue. These data provide evidence that in vivo there are multiple sites other than the epidermis of constitutive IL-1 alpha, IL-1 beta, and TNF-alpha gene transcription in normal human skin.