We tested transcriptional responses to ultraviolet radiation in epidermal keratinocytes using microarray chips containing more than 700 neuroendocrine-immune-related genes. The gene expression pattern was nonrandom and time-dependent; it included increased expression of genes involved in water and salt balance, prostaglandin synthesis, keratinocyte differentiation as well as genes coding for stress effectors, cytokines and metalloproteinases (MMPs). In contrast, expression was decreased for genes coding for growth factors and their receptors and for elements of extracellular matrix. This pattern suggests that transcriptional responses are coordinated and aimed at the preservation of epidermal barrier function, prevention of early carcinogenic events and remodeling of extracellular matrix. In summary, we have developed a microarray chip that can be used for simultaneous testing of transcriptional responses to cutaneous stressors in the context of neuroendocrine-immune functions of the skin. © 2004 Elsevier B.V. All rights reserved.