Maturational changes have been noted in neurally-mediated contractile and relaxant responses in airways from New Zealand White rabbits. In this study, we focused on prostaglandins with bronchoprotective properties as potential modulators of airway tone in maturing rabbits. Tracheal rings from 1-, 2-, and 13-week old rabbits were assessed for neurally-mediated contractile and relaxant responses produced by electrical field stimulation (EFS) of nerves in the presence and absence of the prostaglandin inhibitor, indomethacin (Indo). We also measured EFS-induced release of prostaglandin E₂ (PGE₂) and the stable metabolite of prostacyclin, 6-keto-prostaglandin F₁ (6-keto-PGF₁). In the presence of Indo, EFS produced significant increases in contractile responses in segments from 1- and 2-week old animals, but not in segments from 13-week adult rabbits. Tracheal rings from 1- and 2-week old animals precontracted with neurokinin A (NKA) relaxed 100% in response to EFS when Indo was not in the bath. In rings from 13-week old animals, relaxation was 40%. With Indo, relaxation was abolished in 1-week old animals and reduced to 30% in the 2- and 13-week old groups. Buffer from baths collected after EFS had significant increases in PGE₂ and 6-keto-PGF₁ released from tissues from 1- vs 2- and 13-week old animals. Dose response curves to PGE₂ using tissues precontracted to NKA showed significant increases in relaxant responses in 1- and 2- versus 13-week old rabbits. In rabbit airways, this study demonstrates enhanced modulation of airway tone by PGE₂ plus greater release of the bronchoprotective prostaglandins PGE₂ and prostacyclin early in life.