BACKGROUND: Measurement of P CO 2 is vital in determining effective alveolar ventilation. However, obtaining capillary P CO 2 by a skin prick of the earlobe is painful, and nocturnal measurements disturb sleep. End-expiratory measurement of P CO 2 is also well established, but there is a low precision in predicting arterial or capillary CO 2 . The purpose of the study was to evaluate nocturnal measurement of noninvasive, transcutaneous P CO 2 (P tcCO 2 ) measurement in hypercapnic subjects. METHODS: In this prospective study, 31 subjects with chronic hypercapnic failure-in a stable phase of the underlying disease-and a control group of 12 healthy volunteers were included. Transcutaneous measurements were taken by the Tosca sensor (Radiometer, Copenhagen, Denmark) over a period of at least 6 h during the night. A capillary blood gas was measured at midnight and 4:00 am. RESULTS: The mean nocturnal capillary P CO 2 (P capCO 2 ) of subjects was 50.6 ؎ 10.2 mm Hg. In the 31 subjects with known hypercapnic respiratory failure, the correlation between P tcCO 2 and P capCO 2 at midnight was 0.86 and at 4:00 am r ؍ 0.80. The bias of the hypercapnic subjects was d ؍ ؉ 4.5 with a limit(s) of agreement of 2 SD ؍ 13.0. The process of blood sampling caused no significant change in P tcCO 2 . CONCLUSIONS: Our study evaluated transcutaneous capnography as a continuous nocturnal measurement in hypercapnic subjects. We found a good agreement between the methods. Because CO 2 is not constant in patients with respiratory failure, but instead fluctuates, we would recommend the continuous transcutaneous measurement of P CO 2 as our method of choice in the diagnosis of nocturnal hypercapnia.