Physiological sensations and discomfort constitute the major symptoms reported by aviophobics. Anxiety sensitivity (AS) seems to moderate the relationship between self-reported somatic sensations and flight anxiety, and AS has been identified as a vulnerability factor for flight phobia. In this study we examined whether AS moderates the effects of somatic sensations and autonomic nervous system reactivity on flight anxiety induced by real flight. In fifty aviophobics participating in Cognitive Behaviour Group Therapy (CBGT), flight anxiety, somatic sensations and autonomic nervous system reactivity were assessed during a guided return flight. Results indicate that physiological reactivity interacted with AS. Changes in heart rate and parasympathetic activity were more strongly associated with changes in reported flight anxiety for high AS participants, and less for participants low on AS. Results did not indicate a moderating effect of AS on the relationship between self-reported somatic sensations and flight anxiety. Our results suggest that therapy for flight phobia might benefit from addressing the physical effect of anxiety, by means of cognitive restructuring and exposure to interoceptive stimuli, particularly in aviophobics high in AS.