To determine whether end-tidal PCO2 (PETCO2) measurements obtained with two infrared capnometers accurately approximates the arterial PCO2 (PaCO2) in critically ill neonates, simultaneous measurements of PETCO2 were obtained from the distal and proximal ends of the tracheal tube with a sidestream capnometer (Puritan Bennett/Datex--BP/D) and from the proximal end with a mainstream capnometer (Hewlett-Packard-HP) in 20 intubated neonates. Distal sidestream PETCO2 and mainstream PETCO2 correlated with the PaCO2 (r2 = 0.66 and 0.61, respectively) within the range of 26-57 mmHg PaCO2. However, proximal PETCO2 with the sidestream capnometer correlated very poorly (r2 = 0.09) with PaCO2. The slope of the least square regression line for the distal sidestream capnometer, 0.67, was significantly less than that for the mainstream capnometer, 0.78 but both were significantly greater than that for the proximal sidestream capnometer, 0.39 (P less than 0.05). The slope of the regression for the proximal sidestream capnometer did not differ significantly from horizontal. Insertion of the mainstream sensor for the HP capnometer significantly increased the transcutaneous CO2 when compared with preinsertion values. We conclude that both distal sidestream and mainstream capnometry provide accurate estimates of the PaCO2 in critically ill neonates.