OBJECTIVE To study the relationship between oxygen (O2) delivery (DO2) and O2 consumption (VO2) in surfactant-depleted newborn piglets. METHODS Prospective animal study. METHODS Hospital surgical research laboratory. METHODS Twenty-six anesthetized and ventilated newborn piglets. METHODS Twenty of the animals were subjected to repeated saline lung lavages, and then assigned to either the saline group or the L-NAME group. The other six animals without lavage were studied as the control group. Piglets in the L-NAME group and the control group received 3 mg/kg of N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) i.v.; and those in the saline group received the same volume of saline i.v. RESULTS Cardiac output (CO) was measured and arterial and mixed venous blood gases were analyzed. DO2, O2 extraction ratio (O2ER) and VO2 were calculated. Plasma hypoxanthine was analyzed. In the lung lavaged groups, cardiac index, DO2 and VO2 decreased significantly after L-NAME i.v. but not after saline i.v. Further, the decrease in VO2 in the L-NAME group correlated with the decrease in DO2 (r = 0.83, p < 0.001). In the control group, cardiac index and DO2, but not VO2, decreased significantly after L-NAME i.v. Simultaneously, O2ER increased significantly. Plasma hypoxanthine was not modified by lung lavage but increased after L-NAME i.v. in both the L-NAME and control groups. CONCLUSIONS These data suggest that O2 supply dependency is present in surfactant-depleted newborn piglets.