Infants with respiratory distress syndrome (RDS) have insufficient surfactant systems and decreased functional residual capacity (FRC). This study attempts to relate FRC with severity of disease course. Measurements were made on 36 newborn infants with clinically diagnosed RDS. All infants were intubated and breathing on continuous positive airway pressure (CPAP) at the time studied. Infant CPAP levels were adjusted to 10 cm H2O; then FRC and arterial blood gas measurements were made. The infants were grouped according to their FRC per birth weight (BW). Volumes ≥ 2 SD (≥ 42 ml/kg) of normal term infants not on CPAP were placed in the “large FRC” group. Volumes within ± 2 SD (15–41 ml/kg) were in the “medium FRC” group, and infants ≤ 2 SD (< 14 ml/kg) of normal were in the "small FRC" group. The severity of RDS disease course was judged by the time duration the infants were managed on CPAP and FIO2> 0.21 and by the maximum CPAP and FIO2levels used. Twelve infants (33%) had small FRC, 18 (50%) medium FRC, and 6 (17%) large FRC. The time duration the infants with large FRC were on CPAP was significantly less than infants with medium FRC and the medium FRC group time was less than the small FRC group. The time duration on increased FIO2and maximum FIO2level used on the large FRC group was less than the medium and small FRC groups. Thus, FRC/BW appears related to the severity of RDS disease course. It is possible that the infants with FRC/BW ≥ 42 ml/kg had pneumonia and were misdiagnosed as RDS. If so, FRC monitoring could have assisted in their diagnosis. BW and gestational ages of the groups were not different. Thus, variables other than these two play an important role in the degree of atelectasis occurring in infants with RDS. In patient management, where frequent changes in airway pressure and FIO2are made, knowing the FRC/BW as well as blood gas values could aid the clinician in his choice of CPAP and FIO2levels.