Although there is a strong rationale for the assessment of the subdivisions of lung volume, lung function testing has focused on the measurement of FRC alone in ventilated infants and children. To assess the feasibility, reproducibility, and accuracy of measurements of total lung capacity (TLC), FRC, and their ratio, we determined both lung volumes in 50 critically ill, intubated, and paralyzed infants (mean age [SEM]), 19.9 [4.6] mo) with a variety of lung diseases, by a modified N2 washout technique from end-exhalation and from +40 cm H2O inspiratory pressure, respectively. In the same infants, we also defined TLC by adding inspiratory capacity, measured by pneumotachograph during a passive exhalation from +40 cm H2O to FRC measured by N2 washout. Respiratory mechanics were measured by single-breath occlusion, and the patients were classified according to clinical picture and lung function into groups without lung disease or with restrictive or obstructive disease. The TLC data obtained by both methods showed good agreement for the infants without lung disease or restrictive disease (limits of agreement [LOA]: -3.8/4.6 and -2.9/3.2 ml/kg, respectively). The agreement was less in the infants with airflow obstruction where the N2 washout gave slightly higher values (LOA: -7.1/11.3 ml/kg). Mean FRC/TLC was significantly elevated in the obstructive group, whereas mean FRC alone did not differ from the group without lung disease. Our results suggest that TLC can be measured by both methods in intubated infants, but with limited agreement in obstructive disease. FRC/TLC ratios allow an estimation of the degree of pulmonary hyperinflation.