Acne vulgaris is one of the commonest dermatological diseases,which has a mulifactorial pathogenesis. Clinical experiences shows stressas a factor affecting the course of the disease. As it usually has a chroniccourse, the possibility of the psychological co-morbidities with acneincreases, depression and anxiety are the most common forms of thesepsychological disturbances. So the relation between stress and acne isbidirectional and may put the patients in a vicious cycle. To investigate the role of Substance P (as one of the stressneuromediators) and its receptor NK1R in the aetiopathogenesis of acne. A cases control study, thirty patients with acne, recruited from KasrAl Ainy Hospital outpatient clinic, were enrolled. Two skin biopsies fromthe back were taken (comedonal and inflammatory lesions), the studyalso included twenty healthy subjects as control, immunohistochemicalexamination for the expression of substance p and neurokinin 1 receptor in the skin biopsies were done. All skin biopsies of patients showed positive expression ofsubstance p and neurokinin 1 receptor in both types of acne lesions(comedonal and inflammatory) while sebocytes of control subjects 2 of 20only showed mile positive staining and 18 showed negative staining. In conclusion, SP and its receptor NK1R seems to be important inthe regulation of sebaceous gland function and provide a new vision ofthe participation of the cutaneous nervous system in the pathogenesis ofacne.