The present investigation examined the singular and interactive effects of anxiety sensitivity and perceived control over anxiety-related events in the prediction of panic symptoms using a CO(2)-enriched air biological challenge. Two hundred and twenty-nine adult participants (M(age)=21.02, SD=7.55, 124 females) were recruited from the greater Burlington, Vermont community. Results indicated that pre-challenge anxiety sensitivity, but not perceived control over anxiety-related events, significantly predicted post-challenge panic attack symptoms, anxiety focused on bodily sensations, and, interest in returning for another challenge (behavioral avoidance). In regard to physiological findings, anxiety sensitivity was significantly related to skin conductance level whereas perceived control over anxiety-related events was related to respiration rate. Neither anxiety sensitivity nor perceived control over anxiety-related events was related to heart rate. There also were no interactive effects between anxiety sensitivity and perceived control over anxiety-related events for any of the studied dependent variables. Results are discussed in relation to multi-risk factor models of cognitive vulnerability for panic psychopathology.