Aerosolized iloprost is now used as a therapeutic option in the treatment of pulmonary hypertension. We report on the administration of this derivative of prostacycline in treating severe pulmonary hypertension of the newborn. The combination of iloprost instilled endotracheally and inhaled was chosen as a last attempt at treatment in a critically ill patient who did not respond to advanced conventional treatments, including high frequency oscillation and inhalation of nitric oxide. The use of iloprost converted permanently the right-to-left shunting, leading to a substantial improvement in oxygenation.