Ojective., By constraining the heart, the chest wall, lungs, and pericardium limit diastolic filling and thus have a major role in determining cardiac output. Although intermittent positive pressure ventilation and the application of positive end-expiratory pressure amplifies this constraint, no clinical method exists to assess the impact that positive end-expiratory pressure has on ventricular constraint in the newborn. In this study, we tested the hypothesis that a change in right atrial pressure (Pra) reflects the change in ventricular constraint associated with a change in airway pressure. Design., Experimental, comparative animal study. Setting., Ritchie Centre for Baby Health Research cardiovascular laboratory. Subjects., Neonatal (4-wk-old, n = 6) and newborn (3-day-old, n = 6) Merino/Border-Leicester cross lambs. Interventions. Lambs were anesthetized (alpha-chloralose and ketamine), ventilated, and instrumented to record Pra, thoracic inferior vena caval pressure (Pivc, saline-filled catheters), and pericardial pressure (Pper, liquid-containing balloon). Measurements and Main Results. Changes (Delta) in Pra, Pivc, and Pper were assessed while airway pressure was rapidly reduced from four set levels of continuous positive airway pressure (2.5, 5, 7.5, and 15 cm H2O) to atmospheric pressure. A strong linear relationship was observed between DeltaPra and DeltaPper (DeltaPra = 0.90 DeltaPper - 0.02, r(2) =.98), and between DeltaPivc and DeltaPper (DeltaPivc = 0.86 DeltaPper - 0.02, r(2) =.98) in both the 4-wk-old lambs and the 3-day-old lambs. Conclusions: Our experiments demonstrate that, in the newborn and neonatal lamb, DeltaPra provides an accurate measure of the change in ventricular constraint that accompanies a change in airway pressure, and thus may provide a means of quantifying the magnitude of ventricular constraint imposed by positive endexpiratory pressure and mechanical ventilation during neonatal intensive care.