Severe persistent pulmonary hypertension of the newborn (PPHN) remains a significant cause of neonatal morbidity and mortality with limited effective treatment options. We present the first case of a neonate with PPHN treated concurrently with inhaled nitric oxide (iNO) and intravenous prostacyclin (PGI2). He ultimately was diagnosed with alveolar-capillary dysplasia, a rare and fatal cause of pulmonary hypertension. However, his partial response to treatment demonstrates a possible role for combined therapy with iNO and PGI2 in infants with severe PPHN.