This study examines the validity of a brief screening tool for adolescent panic disorder (PD) in a primary care setting. A total of 165 participants (ages 12-17 years) seen in two pediatric primary care clinics completed the Autonomic Nervous System Questionnaire (ANS; Stein et al. in Psychosomatic Med 61:359-364, 40). A subset of those screening positive (n = 22) and negative (n = 23) for panic symptoms on the ANS completed follow-up phone interviews assessing fit with DSM-IV criteria for panic disorder, self-reported anxiety and depression symptom severity, anxiety-related correlates, and functional impairment. A two-question version of the ANS demonstrated excellent sensitivity (Se = 1.00), but lower specificity (Sp = 0.47) for PD diagnostic status. Three-question and five-question versions modestly improved specificity (Sp = 0.57 and 0.65, respectively). In addition, screen-positive participants reported higher panic symptoms, anxiety sensitivity, and functional impairment, relative to screen-negative participants. Preliminary results suggest the ANS may be a valid screening tool for PD among adolescents, while simultaneously being brief and easy to score. Replication with larger samples is recommended as one related future research endeavor.