We investigated the effects of positive end-expiratory pressure (PEEP) and tidal volume (V T) on lung aeration, pulmonary mechanics, and the distribution of ventilation immediately after birth using a preterm rabbit model.Methods:Sixty preterm rabbits (27 d) received volume-targeted positive pressure ventilation from birth, with one of the 12 combinations of PEEP (0, 5, 8, or 10 cmH 2 O) and V T (4, 8, or 12 ml/kg). Outcomes included functional residual capacity (FRC), peak inflating pressure (PIP), dynamic compliance (Cd), and distribution of ventilation.Results:Increasing PEEP from 0 to 10 cmH 2 O increased FRC by 4 ml/kg, increased Cd by 0.2 ml/kg/cmH 2 O, and reduced PIP by 5 cmH 2 O. Increasing V T from 4 to 12 ml/kg increased FRC by 2 ml/kg, increased Cd by 0.3 ml/kg/cmH 2 O, and increased PIP by 4 cmH 2 O. No effect of V T on FRC occurred at 0 or 5 PEEP, and no effect of PEEP occurred at V T = 4 ml/kg. At 0 PEEP, increasing V T increased the proportion of gas entering the smaller apical regions, whereas at 10 PEEP, increasing V T increased the proportion of gas entering basal regions, from 47 to 63 .Conclusion:Both PEEP and V T have independent, additive effects on FRC, lung mechanics, and the distribution of ventilation during the immediate newborn period.