During mechanical ventilation, inadvertent positive end-expiratory pressure (PEEP) can have deleterious effects, including decreasing lung compliance and alveolar ventilation. To detect and quantitate inadvertent PEEP in 10 preterm neonates receiving mechanical ventilation, we clamped the connection between the endotracheal tube and the respirator at end-expiration and, after about 5 seconds, measured the airway pressure resulting from the trapped gas that emptied into the airways and the measuring system. To study the effect of decreasing inadvertent PEEP on lung mechanics and gas exchange, we measured the compliance of the respiratory system and blood gases. Inadvertent PEEP greater than 1 cm H2O was detected in 19 of 29 measurements. Decreasing inadvertent PEEP by lengthening the expiratory time increased the compliance of the respiratory system (r = -0.74, n = 10, P less than 0.02). Decreasing inadvertent PEEP by greater than 1 cm H2O (mean 2.1 +/- 0.8 cm H2O) in six newborn infants increased respiratory compliance from 0.57 +/- 0.09 to 0.73 +/- 0.13 ml/cm H2O, or approximately 30%, and lowered Pco2 from 40.6 +/- 14.4 to 38.2 +/- 14.1 mm Hg despite a reduction in the level of ventilation set on the respirator. Knowing the amount of inadvertent PEEP and its effects can help improve mechanical ventilation in newborn infants.