Sildenafil is a pulmonary vasodilator shown to be effective in neonates, but conflicting data exist regarding its effect on arterial oxygenation. To address this issue, we tested the sildenafil effect on the piglet's hypoxic pulmonary vasoconstriction (HPV) response. A segmental lung atelectasis was created by obstructing the corresponding bronchus. Total pulmonary and specific flows to the atelectatic and contra-lateral lobes were measured by magnetic resonance (MR) before and 30-min post sildenafil (0.2 and 1 mg/kg i.v.) or saline administration. Flow was reduced (p < 0.01) in the atelectatic and increased in the contra-lateral lobe indicating an effective HPV response. Sildenafil at both doses significantly (p < 0.01) increased flow solely to the atelectatic lobe. At a dose of 1 mg/kg, sildenafil induced a decrease in Pao2 from 285 +/- 37 to 161 +/- 22 mm Hg (p < 0.01). We conclude that the HPV response in the newborn is capable of almost completely reducing blood flow to nonventilated lung units and is reversed following sildenafil i.v. administration in a dose-dependent manner. In the presence of lung parenchymal disease, the use of i.v. sildenafil as a pulmonary vasodilator may worsen arterial oxygenation by reversing the HPV response in nonventilated lung units.