The authors compared Paco2, with end-tidal CO2(ETco2,) sampled at multiple sites along the endotracheal tube (ETT) in seven anesthetized rabbits (weight, 2.7–3.6 kg) to determine the most convenient, yet accurate, sampling location. Comparisons were made during spontaneous and controlled ventilation with fresh gas flows (FGF) of two and ten times the minute ventilation using a Mapleson D circuit. An Engstrom Eliza analyzer with a continuous sampling rate of 100 ml/min was used to measure ETCO. A 0.75-mm ID polyethylene tube inserted in the side of the ETT sampled ETco2at the distal tip and at the 6-, 12-, and 15-cm marks on the ETT. ETco2, was also measured at the standard proximal connector. The differences (P< 0.05) between Paco2, and ETCO2at the distal, 6-, 12-, and 15-cm marks were 2.9 ± 0.4, 3.1 ± 0.4, 3.6 ± 0.4, and 4.6 ± 0.5 mmHg (x ± SEM), respectively, and did not change with FGF or mode of ventilation. The difference between Paco2, and ETco2, measured at the proximal connector was always large but significantly (P< 0.05) greater during spontaneous than controlled ventilation (24.2 ±1.5versus15.0 ± 1.4 mmHg) and at higher FGF (19.4 ± 1.3versus16.8 ±1.6 mmHg). The differences (P< 0.05) between ETCO2, at the distal tip and ETco2, at the 6-, 12-, and 15-cm marks were 0.24 ± 0.07, 0.73 ± 0.11, and, 1.77 ± 0.20 mmHg, respectively. This demonstrates that the change in ETco2, between the distal tip and the 12-cm mark on the ETT is less than 1 mmHg, and that this clinically insignificant difference is independent of FGF and mode of ventilation. The 12 cm-mark is outside of the mouth on a newborn, and sampling ETCO2, at that point, which may be accomplished simply by inserting a small needle in the side of the ETT, may be the most appropriate sampling location.