Although psychosocial aspects of skin diseases are well known, disease-specific questionnaires validated for use in clinical trials are not available to assess the impact of facial acne on health-related quality of life or to evaluate therapeutic change. Development of such an instrument was undertaken and included item generation, reduction and pilot-testing phases. By interviewing acne subjects and dermatologists and literature review, 168 possible items were identified. Next, 165 acne subjects identified which items affected them and rated importance on a 5-point scale. Reduction to a brief questionnaire was performed by evaluating patient-perceived importance and factor analysis; four domains were identified (self-perception, role-emotional, role-social, acne symptoms). After pilot-testing for comprehension in acne subjects, further revisions were made to improve clarity and applicability. The resulting instrument takes 10 minutes to complete, and consists of 24 questions assessing how acne affected certain aspects of patients' lives during the past week on a 7-point scale. Thus, an instrument with excellent content validity was developed to assess health-related quality of life in patients with facial acne, and is comprised of statistically meaningful items of importance to patients. Other measurement characteristics are being assessed in a recently initiated study to evaluate test-retest reliability and responsiveness to therapy.