Recent clinical studies have suggested that improvement in pulmonary gas exchange with the use of continuous negative extrathoracic pressure (CNEP) in conjunction with intermittent mandatory ventilation (IMV) may be due to increased pulmonary blood flow. Accordingly, we investigated the effects of CNEP vs positive end-expiratory pressure (PEEP) in ventilated neonatal piglets after Escherichia coli endotoxin was administered to induce pulmonary hypertension. Two experimental groups of piglets with six in each, were subjected to three 30-min alternating periods--6 cm H2O CNEP with 6 cm H2O PEEP, beginning 2 h after endotoxin infusion. End-expiratory lung volume (EELV) increased similarly from baseline (13 +/- 2 mL/kg) with both CNEP (28 +/- 2 mL/kg) and PEEP (29 +/- 2 mL/kg). In addition, the increase in PaO2 from baseline with CNEP (106 +/- 9 to 135 +/- 7 mm Hg) was similar to that with PEEP (114 +/- 11 to 132 +/- 6 mm Hg). Further, no differences were found in dynamic lung compliance, EELV, lung resistance, blood gas indexes, or hemodynamics, including transmural pulmonary artery pressure and pulmonary vascular resistance between CNEP and PEEP. With transpulmonary pressure and transrespiratory pressure equal, CNEP in tandem with IMV is physiologically equivalent to PEEP and IMV.