The aim of this study was to examine the effects of history of suffocation, state-trait anxiety, and anxiety sensitivity on response to a 35% carbon dioxide (CO(2)) challenge in panic disorder patients, their healthy first-degree relatives and healthy comparisons. Thirty-two patients with panic disorder, 32 first-degree relatives, and 34 healthy volunteers underwent the 35% CO(2) challenge. We assessed baseline anxiety with the Anxiety Sensitivity Index (ASI) and State-Trait Anxiety Inventory (STAI1), and panic symptoms with the Panic Symptom List (PSL III-R). A history of suffocation was associated with greater risk of CO(2) reactivity in the combined sample. Patients had more anxiety sensitivity and state and trait anxiety than relatives and healthy comparisons; the difference between relatives and healthy comparisons was not significant. In female patients, trait anxiety predicted CO(2)-induced panic. Having a CO(2)-sensitive panic disorder patient as a first-degree relative did not predict CO(2)-induced panic in a healthy relative. History of suffocation may be an important predictor of CO(2)-induced panic. Trait anxiety may have a gender-specific relation to CO(2) reactivity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.