The sebaceous gland exhibits an independent peripheral endocrine function and expresses receptors for neuropeptides. Previous reports have confirmed the presence of a complete corticotropin-releasing hormone (CRH) system in human sebocytes in vitro. The capability of hypothalamic CRH to induce lipid synthesis, induce steroidogenesis and interact with testosterone and growth hormone implicates a possibility of its involvement in the clinical development of acne. The purpose of the study was to detect expression changes of CRH/CRH binding protein (CRHBP)/CRH receptors (CRHRs) in acne-involved skin, especially in the sebaceous glands. Expression of CRH/CRHBP/CRHRs was analysed by immunohistochemistry in biopsies from facial skin of 33 patients with acne, noninvolved thigh skin of the same patients and normal skin of eight age-matched healthy volunteers. Very strong positive reaction for CRH was observed in acne-involved skin in all types of sebaceous gland cells, irrespective of their differentiation stage, whereas in noninvolved and normal skin sebaceous glands exhibited a weaker CRH staining depending upon the differentiation stage of sebocytes. The strongest reaction for CRHBP in acne-involved sebaceous glands was in differentiating sebocytes. CRHR-1 and CRHR-2 exhibited the strongest expression in sweat glands and sebaceous glands, respectively. Expression of the complete CRH system is abundant in acne-involved skin, especially in the sebaceous glands, possibly activating pathways which affect immune and inflammatory processes leading to the development and stress-induced exacerbation of acne.