Cyclic nucleotides are relaxants of the airway smooth muscle, yet most of the available data were obtained in adult animals. The cyclases expression and activity have been reported to be developmentally regulated in the lung and little is known about the age related changes in their bronchial muscle relaxation potential. We evaluated and compared the newborn and adult rat bronchial smooth muscle response to cyclic AMP- and GMP-dependent agonists in isometric mounted bronchial rings. In acetylcholine pre-contracted bronchial muscle the relaxant response to the cAMP agonist forskolin was not age dependent, but the relaxant response to the nitric oxide (NO) donor sodium nitroprusside (SNP) was significantly greater (P<0.01) in the newborn. To further evaluate the cGMP pathway, we stimulated the soluble guanylate cyclase (sGC) with the specific agonists BAY 41-2272 and YC-1. In keeping with the SNP dose-response curves, the sGC agonists significantly relaxed the newborn, but not the adult bronchial muscle. Protein expression of the sGC ₁ and ₁ subunits were significantly lower (P<0.01) in adult as compared to the newborn bronchial tissue. Consistent with these results, the NO stimulated sGC activity was significantly greater in the newborn as compared with the adult (P<.01). In conclusion, the bronchial smooth muscle cGMP-, but not cAMP-dependent relaxant response is developmentally regulated and significantly reduced in the adult rat.