The effect of postnatal age on norepinephrinc-induccd α2-adrenoreceptor-mediated release of endothelium-derived relaxing factor in porcine intramuscular pulmonary arteries was studied. Rings of pulmonary artery from fetal, newborn, 3-d-, 10-d-, 9-wk-, and 15-wk-old pigs with and without cndothelium were suspended for isometric force measurement in Krebs-Ringer bicarbonate solution (37°C, 95% O2-5% CO2). In 15-and 10-wk-old pigs, norepinephrine increased tone in arteries with and without endothelium but produced relaxations at high concentrations only in arteries with endothelium. These relaxations were not inhibited by the α1-antagonist prazosin but were completely abolished by the α2-antagonist yohimbine and the inhibitor of nitric oxide release N--nitro-L-arginine methyl ester. This confirms that the norepinephrine-induced relaxations were due to α2-mediated release of endothelium-derived relaxing factor. Arteries from only 50% of the 10-d-old animals showed endothclium-dependent relaxations, and at 3 d of age and younger no relaxations were seen. In animals less than 10 d old, only some of the vessels contracted to norepinephrine and the contractile response was diminished compared with 15-wk-old animals, whereas the response to prostaglandin F2α and histamine was similar in the neonatal group (newborn, 3 d old, and 10 d old). This group showed a dose-dependent relaxation to nitric oxide, with 10-d-old animals more sensitive to nitric oxide than newborn animals. Thus, maturational changes occur in adrenergic-mediated contraction, in the modulation of contractility by cndothelial α2-adrenoreceptors and in the response to nitric oxide.