The present investigation examined the relation between discomfort intolerance and panic-relevant symptoms among 216 (117 women) young adults who participated in a biological challenge procedure. Partially consistent with hypotheses, after covarying for anxiety sensitivity, negative affectivity, and emotional acceptance, the intolerance subscale of the Discomfort Intolerance scale [DIS; Schmidt, N. B., Richey, J. A., & Fitzpatrick, K. K. (2006). Discomfort intolerance: development of a construct and measure relevant to panic disorder. Journal of Anxiety Disorders, 20, 263-280] was significantly incrementally related to increased post-challenge anxiety focused on bodily sensations, physical panic symptoms, and behavioral avoidance, but not cognitive panic symptoms. Inconsistent with prediction, the avoidance subscale of the DIS was not significantly related to any of the dependent variables. Results are discussed in relation to better understanding the role of discomfort intolerance as a unique explanatory factor in the context of panic psychopathology.