The purpose of this report is to propose a staged therapeutic protocol for the treatment of persistent pulmonary hypertension of the newborn (PPHN) based on retrospective clinical experience. We analysed the clinical course of 19 term and near-term neonates with severe PPHN treated between 1991 and 1993, before the introduction of inhalational nitric oxide (NO) therapy. Basic therapy consisted of continuous sedation, and analgesia, circulatory support with dobutamine, dopamine and substitution of 5% albumin or packed red blood cells, mechanical hyperventilation, alkalisation with sodium bicarbonate and surfactant instillation. Consecutive therapy included the administration of norepinephrine, high frequency oscillatory ventilation (HFOV), Prostacyclin (PGI2) and extracorporeal membrane oxygenator (ECMO) therapy with entry criteria for each stage of treatment. From our observations we suggest that firstly, an early increase in systemic mean arterial pressure due to norepinephrine and secondly, HFOV trials are beneficial in patients with PPHN. The staged protocol shall be applicable in most neonatal intensive care units in which inhalational NO and ECMO therapies are not available and includes our present entry criteria for both therapies.