[show abstract][hide abstract] ABSTRACT: Dysregulation within both respiratory control systems and the hypothalamic-pituitary adrenal (HPA) axis has been implicated in the pathophysiological of panic disorder. However, potential linkages between respiration and the HPA axis have rarely been examined in panic patients. We have previously published neuroendocrine and psychophysiological response data from a laboratory panic model using the respiratory stimulant doxapram. We now present a new, theoretically driven re-examination of linkages between HPA axis and respiratory measures in this model. Previous analyses showed elevated corticotropin (ACTH) and persistent tidal volume irregularity in panic patients, due to a high frequency of sighs. Regression analyses now show that tidal volume irregularity and sigh frequency were strongly predicted by pre-challenge ACTH levels, but not by subjective distress or panic symptoms. We predicted this relationship on the basis of our hypothesis that both the HPA axis and respiratory control systems may be reactive to contextual cues such as novelty or anticipation of future challenge. Follow-up work is needed to directly test this hypothesis. Depression and Anxiety, 2008. Published 2007 Wiley-Liss, Inc.