AP-2alpha is a member of a family of transcription factors expressed in cells of the epithelial and neural crest lineage. AP-2alpha plays an essential role in embryonic development and in regulation of epithelial gene transcription. To further characterize the role of AP-2alpha in skin biology, we assessed its expression in the skin of C57BL/6J mice during defined stages of hair follicle morphogenesis and cycling. During early hair follicle morphogenesis, AP-2alpha was upregulated in the epidermal placode, in the basal keratinocytes of the hair follicle bud, and then in the inner root sheath. The follicular papilla cells underwent a brief upregulation of AP-2alpha expression during the initiation of hair shaft formation and active hair follicle downward growth. Completion of hair follicle morphogenesis was associated with a marked reduction of AP-2alpha immunoreactivity in the lower portion of the hair follicle including both epithelial and mesenchymal compartments. In adolescent mouse skin, consistently strong AP-2alpha expression was found in the basal keratinocytes of the epidermis, in the hair follicle infundibulum, and in the sebocytes. In the follicular papilla, AP-2alpha was weakly expressed in telogen, significantly upregulated in early anagen, then gradually declined, and reappeared again in middle catagen. In the inner root sheaths, AP-2alpha expression was detected during early and middle anagen and during middle catagen stages. Prominent AP-2alpha expression was also seen in the zone of club hair formation. Therefore, AP-2alpha upregulation in both epithelial and mesenchymal hair follicle compartments was coordinated with initiation of major remodeling processes. Our findings support the use of the hair follicle as a model to explore the role of AP-2alpha in physiologic remodeling of developing organs and in reciprocal ectodermal-mesenchymal interactions.