Neuroticism and extraversion have been linked to the etiologies and course of anxiety and mood disorders, such that neuroticism is broadly associated with numerous disorders and extraversion is most strongly associated with social anxiety and depression. While previous research has established the broad associations between temperament and emotional disorders, less is known about the specific, proximal factors that are associated with them, and very few studies have situated these risk factors into a larger etiological model that specifies how they may relate to one another. The current study examined the interaction of extraversion and anxiety sensitivity (AS) in predicting social anxiety symptoms in a large, diagnostically diverse clinical sample (N=826). Symptoms were assessed with self-report and dimensional interview measures, and regression analyses were performed examining the main effects and interaction of extraversion and AS (examining both total and lower-order components) on social anxiety. Results showed that at higher levels of AS, the inverse relationship between extraversion and social anxiety was stronger, and the social concerns component of AS is responsible for this effect. This interaction was also observed with regard to depression symptoms, but the interaction was not present after accounting for shared variance (i.e., comorbidity) between depression and social anxiety symptoms. Clinical and theoretical implications of the results are discussed.