Objective: To investigate the suitability of volumetric capnography for assessing alveolar gas exchange in very small, surfactant- depleted lungs. Design: Prospective animal trial. Settings: Animal laboratory in a university setting. Subjects: Twenty-one ventilated newborn piglets (age <12 hrs; median weight, 890 g; range, 560-1435 g). Interventions: Bronchoalveolar lavage with instillation of 30 mL/kg normal saline. Ventilatory, circulatory, and lung mechanic variables were measured before and 0, 30, and 60 mins after bronchoalveolar lavage. Measurements and Main Results: The alveolar deadspace fraction calculated by the Bohr and the Bohr/Enghoff equations increased three-fold (p < .001) after bronchoalveolar lavage in capnograms with distinct alveolar plateau, whereas in capnograms without alveolar plateau no statistical significant difference was seen. The main problem of capnography in small and especially stiff lungs was the high number of discarded records exclusively caused by a missing alveolar plateau. Rates of discarded records of capnography were 9.5% before lavage and increased (p < .01) to 52.4%, 47.6%, and 42.8% after bronchoalveolar lavage (0, 30, and 60 mins). With decreasing exhalation time, the number of discarded records increased significantly. No plateau was seen in >75% of recorded files with exhalation times <200 msecs. The effect of bronchoalveolar lavage on all variables measured was quite different, with the highest impact on required ventilatory settings, calculated oxygenation variables, and compliance. The effect of bronchoalveolar lavage on arterio-alveolar CO₂ difference, CO₂ production, and alveolar deadspace was much lower and statistically significant only in capnograms with alveolar plateau. Conclusions: Volumetric capnography is a useful tool to detect impaired alveolar gas exchange in surfactant-depleted small lungs. However, the method failed if there was no alveolar plateau in the volumetric capnogram especially in stiff lungs with short exhalation times.