Positive end-expiratory pressure (PEEP) is a standard treatment for patients with refractory hypoxemia due to an acute restrictive pathology. The therapeutic range of PEEP can be quite narrow. PEEP therapy has been optimized using invasive variables such as oxygen transport and pulmonary shunt, and noninvasive variables such as compliance; however, the measurements are complex. We constructed a computerized PEEP-optimization system consisting of a Siemens 900C ventilator, Siemens prototype sulfur hexafluoride analyzer, Siemens 940 lung mechanics analyzer, and a DEC 11/ 23 microcomputer. The user may choose from three different noninvasive PEEP titration algorithms: maximizing static total respiratory system compliance (CTR), maximizing functional residual capacity(FRC)-based compliance (CFRC), and normalizing FRC. The device was tested in six dogs with pulmonary injury induced by oleic acid. The system was constrained to 3-cm H2O PEEP steps at 20-min intervals. The algorithm normalizing FRC reached optimal PEEP levels in 40 min, with a mean difference from the desired FRC of 15 ± 48 (SEM) ml. This corresponds to a mean percent error of 1.0% ± 2.63%. The CFRCand CTRalgorithms reached optimal PEEP levels in 60 and 40 min, respectively, and maintained a maximal compliance for 85% of the time. This system provides fully automated noninvasive PEEP titration and is flexible enough to incorporate easily any other PEEP titration algorithms. It should improve patient care by guaranteeing that PEEP therapy is truly optimized throughout the patient's recovery.