Ventilation of immature airways has been shown to result in pressure-induced deformation and alteration of mechanical properties. These changes in mechanical properties may alter the effect of compressive pressures on pressure-flow relationships. To test this hypothesis, unventilated (Group I, n = 8) and ventilated (group II, n = 8; mean pressures of 8-12 cm H2O for 2 h duration) tracheal segments were excised from preterm lambs approximately 118 days gestation and mounted in a Krebs-filled chamber for determination of compliances and pressure-flow relationships. Compliance data were obtained for both the inflation loop (inflation compliance) and the collapsing loop (collapsing compliance) of the pressure-volume curve for each segment. Flow (V = 2-10 liter/min.) was introduced through the lumen of each segment at different chamber pressures (Pc = 5-30 mm Hg). Driving pressure (Pd) was recorded for each V and Pc. Airway resistance (R) was calculated as Pd/V. Group II had significantly greater (p less than 0.005) radii than Group I, suggesting ventilation-induced deformation. Group II had significantly lower (p less than 0.05) inflation compliance but significantly greater (p less than 0.05) collapsing compliance than group I. Two-factor analysis of variance demonstrated significantly greater (p less than 0.05) R in group II at each value of V and each Pc. These data may help to explain the flow limitation and gas-trapping observed in preterm infants who have been mechanically ventilated.