NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4 -10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 Ď« 10 8 CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p Ď˝ 0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p Ď˝ 0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates. Group B Streptococcus (GBS) sepsis is characterized by pulmonary hypertension, arterial hypoxemia, metabolic acidosis, decreased cardiac output (CO), and systemic hypotension progressing sometimes to irreversible shock (1). Despite modern intensive care, this condition continues to carry high morbidity and mortality. Many modalities have been proposed for the management of pulmonary hypertension, including cytokine inhibitors and vasodilators (2-7). However, clinical application of these modalities is limited because of significant side effects and lack of selectivity to the pulmonary vasculature.Inhaled nitric oxide (iNO) has emerged in recent years as an effective and selective treatment modality for pulmonary hypertension. Its effectiveness in treating persistent pulmonary hypertension of the newborn was documented in a number of animal models and also clinical trials (8,9). In animal models of pulmonary hypertension induced by GBS sepsis, iNO was