Post-traumatic stress disorder (PTSD) is currently classified as an anxiety disorder in DSM-IV, and as a neurosis or stress-related disorder in ICD-10. It shares many features with depression. Sensitivity to carbon dioxide (CO2), a classic provocation agent in the proto-typical anxiety disorder, panic disorder, has not been tested in PTSD. Twenty rigorously ascertained drug-naïve subjects with PTSD inhaled a single vital capacity inhalation of 35% CO2; before and after the inhalation they completed measures of PTSD and panic anxiety, and were rated for the presence of a panic attack. These results were retrospectively compared with those of 39 healthy volunteers and 17 patients with panic disorder previously studied by the same research group. PTSD symptoms were not exacerbated by CO2. Two out of twenty PTSD subjects panicked. PTSD subjects' responses were indistinguishable from those of healthy volunteers, and differed from those of subjects with panic disorder. The lack of sensitivity to carbon dioxide in PTSD subjects in the present study adds to the literature on the differences between PTSD and other anxiety disorders, and to that on the specificity of the CO2 challenge in panic disorder.