The purposes of this study were to determine the effects of positive end-expiratory pressure (PEEP) and end-expiratory lung volume on systemic blood flow, whether PEEP levels yielding maximum systemic oxygen transport are associated with maximum lung compliance, and the effects of end-expiratory lung volume on pulmonary resistance to gas flow, in an animal model of respiratory distress. Twelve cats were inoculated with 12 mg/kg N-Nitroso N-Methylurethane (NNNMU) to induce respiratory distress. The NNNMU caused a 76% decrease in disaturated phosphatidyl-choline of lung lavage, a 34% decrease in functional residual capacity (FRC), an 80% decrease in lung compliance, an 88% increase in pulmonary resistance to gas flow, a 43% decrease in PaO2, and a 37% decrease in oxygen consumption. Systemic blood flow and systemic oxygen transport were not significantly altered by the chemically induced respiratory distress. PEEP levels of 5.1 +/- 0.8 cm H2O returned end-expiratory lung volume to normal FRC levels. Increases in PEEP caused systemic blood flow to decrease even when end-expiratory lung volume was below or equal to normal FRC levels but did not significantly affect systemic oxygen transport, lung compliance, or pulmonary resistance. We conclude that in cats with NNNMU-induced respiratory distress: PEEP causes decreases in systemic blood flow, lung compliance and systemic oxygen transport are not clear indicators of optimal PEEP level, and returning end-expiratory lung volume to normal FRC does not significantly reduce pulmonary resistance to gas flow.