To study the effect of prostacyclin treatment on pulmonary arterial pressure (PAP), systolic pressure (BP), and systemic oxygenation, eight infants with persistent pulmonary hypertension of the newborn (PPHN) born between 34 and 42 weeks' gestation and having a birth weight of 2540-4130 g were studied using Doppler echocardiography. At a mean age of 19 hours (range 3-32 hours), despite maximal ventilator therapy and an FIO2 of 1.0, the mean PaO2/PAO2 was 0.07 (range 0.04-0.09) and the AaDO2 was 616 mmHg (range 521-654 mmHg). After volume correction and during inotropic medication with dopamine and dobutamine, the mean PAP by echocardiography was 68.6 +/- 6.5 mmHg and the mean BP 59.8 +/- 4.8 mmHg. Prostacyclin infusion was then started at a dose of 20 ng/kg/min and increased stepwise to a mean dose of 60 ng/kg/min (range 30-120 ng/kg/min) over 4-12 hours, at which time PAP decreased to 49.2 +/- 3.5 mmHg (p = 0.0005) and BP to 53.2 +/- 9.1 mmHg (p = 0.17); the PAP thereafter remained below the BP. After 72 hours of prostacyclin infusion, PAP was 49.6 +/- 18 mmHg, BP 66.1 +/- 5.4 mmHg, PaO2/PAO2 0.14 +/- 0.12, and AaDO2 428 +/- 189 mmHg at FIO2 0.65. The median duration of prostacyclin infusion was 3.6 days and of respirator treatment 7.0 days. All patients survived without extracorporeal membrane oxygenation. At 6-12 months, none of the patients had severe central nervous system complications, but two had bronchopulmonary dysplasia. These findings indicate that prostacyclin is able to reverse the right-to-left shunt in PPHN by decreasing PAP, and that systemic hypotension can be prevented with adequate volume correction and inotropic medication.