The NO/cGMP pathway plays a key role in the regulation of pulmonary vascular tone during the transition from the fetal to the neonatal circulation and it is impaired in pathophysiological conditions such as pulmonary hypertension. In the present study, we have analyzed the changes in the function and expression of sGC in pulmonary arteries during the early postnatal maturation in isolated third branch pulmonary arteries from newborn (3-18 h of age) and 2 week old piglets. The expression of sGC 1 subunit in pulmonary arteries increased with postnatal age both at the level of mRNA and protein. The catalytic region of porcine sGC 1 was sequenced, showing a 92% homology with the human sequence. This age-dependent increase in sGC expression correlated with increased vasorelaxant responses to the physiologic sGC activator NO and to the exogenous sGC activator YC-1, but not to the membrane permeable cGMP analogue 8-bromo-cGMP. In conclusion, an increased expression of sGC in pulmonary conduit arteries from two week old as compared to newborn piglets explains, at least partly, the age-dependent increase in the vasorelaxant response of NO and other activators of sGC.