Severe neonatal aspiration of meconium is frequently complicated by fatal pulmonary hypertension. The protective effect of an i.v. bolus of methylprednisolone on meconium aspiration-induced hypertensive lung injury was studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator settings were adjusted to keep arterial Po2above 8 kPa and arterial Pco2below 5 kPa. Meconium insufflation induced a biphasic pulmonary pressor response during the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h) increase in pulmonary artery pressure and inhibited significantly the second phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary vascular resistance. This inhibition of resistance increase was most profound in the postarterial segment of the lung circulation, as determined by pulmonary artery occlusion. Additionally, the methylprednisolone pretreated group demonstrated a significant decrease in venous admixture together with improved oxygenation during the late phase after the insult, and further showed evidence of diminished lung edema formation. Although meconium aspiration-induced fall in blood leukocyte concentration was inhibited by methylprednisolone pretreatment, no histologic difference was found in pulmonary leukocyte sequestration. Our results thus show that in adapted porcine lungs methylprednisolone pretreatment improves oxygenation and attenuates the meconium aspiration-induced pulmonary hypertensive response by preventing the increase in the postarterial resistance.Abbreviations: MPAP,mean pulmonary artery pressure;PWP,pulmonary wedge pressure;CVP,central venous pressure;PAOP,pulmonary arterial occlusion pressure;MABP,mean arterial blood pressure;CO,cardiac output;PVR,pulmonary vascular resistance;Ra, pulmonary arterial resistance;Rv, pulmonary postarterial resistance;˙Qva/˙Qt, venous admixture;Fio2, fraction of inspired oxygen