The vast majority of biological challenge studies have focused on panic disorder though there is a small literature suggesting that patients with social anxiety disorder (SAD) show comparable responding. The SAD literature is potentially confounded, however, by the fact that many patients with SAD experience panic attacks. These patients also show elevated negative affect and anxiety sensitivity, factors that are also associated with increased fear responding to challenge. By controlling for these factors, the present report was able to evaluate whether social anxiety symptoms were uniquely associated with fearful responding to a 35% CO(2) challenge. A large nonclinical sample of young adults (N=120) screened for a history of panic attacks completed a 35% CO(2) challenge. Those high (versus low) in social anxiety showed approximately 2.5 times greater risk for experiencing substantial increases in anxiety in response to the challenge. This significant association was maintained after controlling for anxiety sensitivity and general negative affect. These data provide novel evidence suggesting that social anxiety symptoms are uniquely associated with anxious responding to 35% CO(2) challenge and this sensitivity appears to precede the development of panic attacks.