Surfactant protein A (SP-A), the major hydrophilic protein specifically associated with surfactant, has multiple metabolic and host defense functions as well as primary surfactant biophysical functions in association with the other surfactant proteins and lipids. To characterize its kinetics of secretion and clearance from the airspace, we measured specific activity-time curves for alveolar and lamellar body associated SP-A following the intravascular and/or intratracheal administration of the radiolabeled precursors Tran 35S-label containing primarily methionine and cysteine or [3H]methionine to newborn and adult rabbits. Alveolar SP-A specific activity peaked 30 min after precursor injection in both newborn and adult rabbits, and labeled SP-A was not detected in lamellar bodies until after 2 h. In newborns, a second peak of labeled SP-A appeared at 15 h. In both newborns and adult rabbits, lamellar body specific activity-time curves were most consistent with SP-A entering lamellar bodies via a recycling pathway from the airspaces. The airspace clearance of SP-A in adult rabbits had a biologic half-life of about 4.5 h. There was very little decrease in SP-A specific activity in the newborn rabbits, indicating minimal catabolism. These studies demonstrate secretion of endogenously synthesized SP-A by a pathway separate from lamellar bodies. The kinetics of secretion of SP-A and the surfactant phospholipid in newborn and adult rabbits indicate separate metabolic pathways.