Maturational changes of the contractile properties of airway smooth muscle have been suggested to occur during the late prenatal and early postnatal period in the piglet. However, the timing and mechanisms involved remain elusive. Therefore, we studied isometric contraction of tracheal smooth muscle (TSM) to evaluate the effects of maturation on 1) the response of TSM to the muscarinic agonist acetylcholine (Ach); and 2) the regulatory activity of acetylcholinesterase (AChE) during the early postnatal period in the piglet. Studies were performed in 1-5-day-old (n = 6) and 14-22-day-old (n = 8) anesthetized, mechanically ventilated piglets. Changes in tracheal tension were measured in vivo from an open tracheal segment and normalized for both longitudinal length of the tracheal segment and cross-sectional area. Dose-response curves to locally applied Ach were obtained before and after the intravenous administration of the AChE inhibitor physostigmine (Phys). Ach-induced changes in tracheal tension significantly increased with maturation during the first 3 weeks of life (P < 0.01), regardless of normalization method. The addition of Phys significantly increased the cholinergic responses of TSM in both age groups (P < 0.02). However, this increase was comparable between age groups. There was also no difference in AChE activity measured in tracheal smooth muscle homogenates between the 1-5 and 14-22-day-old animals. These data indicate that maturation significantly enhances the cholinergic responses of tracheal smooth muscle in the early postnatal period in the piglet.(ABSTRACT TRUNCATED AT 250 WORDS)