Postnatal adaptation of the pulmonary circulation is mediated by endothelium-derived nitric oxide (EDNO). Recent studies have demonstrated that inhaled nitric oxide (NO) causes selective and sustained vasodilation in infants with PPHN. The short half-life of NO limits its clinical application. We hypothesized that aerosol delivery of a NO-adduct, diethylenetriamine(DeTANO), can cause sustained and selective pulmonary vasodilation. To test this hypothesis, we studied the pulmonary vascular response of late-gestation fetal lambs (n=7; age=138 days; term = 147) to aerosolized DeTANO in the presence of an EDNO inhibitor, nitro-L-arginine (L-NA). At surgery, an ultrasonic flow transducer was placed on the left pulmonary artery (LPA) to measure flow (Q). Pressures were measured with catheters in the main pulmonary artery and aorta. After baseline measurements, L-NA (1 mg/min × 30 min) was infused into the LPA prior to ventilation (VENT) with 100% O2 for 30 minutes, followed by continued VENT with 10% O2 for 10 min. This represents the control period. VENT was continued with 100% O2 and DeTANO was given in doses of 0.1, 0.4, and 1.0 mg. 15 minutes following the last dose of DeTANO animals were ventilated with 10% O2.In the control period, after VENT with 100% total pulmonary resistance (TPR) was 0.724±.26 mmHg/cc/min. During VENT with 10% O2, TPR increased by 0.115±.068mmHg/cc/min. Aerosol delivery of DeTANO 0.1mg decreased TPR from 1.075±0.144 to 0.497±0.038 (p<0.05). After DeTANO, TPR did not change during VENT with 10% O2 (p<0.05, compared to control period. Aortic pressure did not change with DeTANO. We conclude that DeTANO can cause selective and sustained fetal pulmonary vasodilation. Aerosol delivery of DeTANO may increase the clinical applications of NO.