Recent studies have shown that end-tidal PCO(2) is lower during anxiety and stress, and that changing PCO(2) by altering breathing is therapeutic in panic disorder. However, end-tidal estimation of arterial PCO(2) has drawbacks that might be avoided by the transcutaneous measurement method. Here we compare transcutaneous and end-tidal PCO(2) under different breathing conditions in order to evaluate these methods in terms of their comparability and usability. Healthy volunteers performed two hypoventilation (slow vs. paused breathing) and two hyperventilation tests (25 mm Hg at 18 vs. 30 breaths per minute). Three measurements of PCO(2) (two end-tidal and one transcutaneous device), tidal volume, and respiration rate were recorded. Before and after each test, subjects filled out a symptom questionnaire. The results show that PCO(2) estimated by the two methods was comparable except that for transcutaneous measurement registration of changes in PCO(2) was delayed and absolute levels were much higher. Both methods documented that paused breathing was effective for raising PCO(2), a presumed antidote for anxious hyperventilation. We conclude that since the two methods give comparable results choosing between them for specific applications is principally a matter of whether the time lag of the transcutaneous method is acceptable.