Acne is a common chronic disorder of the pilosebaceous unit that has a complex etiology. There is evidence that neurogenic factors, such as substance P, may be involved in the pathogenesis of acne. Substance P is a neuropeptide that has, among others, proinflammatory and immunomodulatory effects and that can be secreted by cutaneous nerves, and is known to be released in response to stress. Thirty-four males were the subjects of the present study, 19 patients with acne of the back and 15 age-matched healthy controls. We have found that 57.9% of patients readily report exacerbation of their acne by stress, and using a 90-item questionnaire we have shown that 52.7% of patients have psychological affection in the form of anxiety, depression or social isolation. Using immunohistochemistry we compared the presence of substance P in the skin of patients, non-lesional and lesional, and of controls. Results show that there is a definite difference in the intensity and pattern of distribution of substance P between controls and patients. Nerves around sebaceous units in specimens from patients show strong staining of substance P compared to control specimens and the difference is significant (P .002), also sebocytes in patients show higher positivity to substance P than controls (P .026). Results suggest that substance P is involved in the pathogenesis of acne. This might partially shed light on the significance of neurogenic and psychogenic aspects in the disease process.