Central or peripheral stress may induce the development of clinical inflammation in the pilosebaceous unit, leading to the development of acne lesions or to exacerbation of pre-existing acne. Melanocortin peptides such as alpha-melanocyte-stimulating hormone and its receptors do not only regulate melanogenesis but can also affect non-pigmentary processes, such as inflammation, apoptosis and sebogenesis. The purpose of the study was to investigate by immunohistochemistry if changes of melanocortin-1 receptor expression exist in acne lesions versus normal skin. In all, 33 patients with acne vulgaris and seven age-matched volunteers without acne participated in the study. Skin biopsies were taken from acne-involved faces, the non-involved thigh skin of the same patients and from normal human skin. Melanocortin-1 receptor immunoreactivity was most prominently detectable in adnexal structures. Sebocytes and keratinocytes of the ductus seboglandularis of acne-involved and non-involved skin showed very intense melanocortin-1 receptor expression in contrast to less intense scattered immunoreactivity in normal skin samples. These data suggest that melanocortin-1 receptor is involved in the pathogenesis of acne.