We measured surfactant protein A (SP-A) by ELISA using a rabbit antihuman SP-A polyclonal antibody and saturated phosphatidylcholine (SPC) by thin-layer chromatography in sequential tracheal fluid samples obtained from 16 preterm neonates without lung disease and 37 with respiratory distress syndrome (RDS). SP-A and SPC were lower in neonates with RDS than in control infants (1.0 +/- 0.1 versus 8.9 +/- 2.2 ng SP-A/microgram protein [p < 0.0001] and 0.20 +/- 0.05 versus 0.70 +/- 0.19 mumol SPC/mg protein [p < 0.01], respectively). Initial SP-A concentrations correlated inversely with severity of RDS (r = 0.45, p < 0.01) but did not correlate with initial SPC levels. Significant increases in SP-A were detectable within 12 to 24 h after birth in neonates with RDS. Further increases occurred subsequently and were similar for neonates treated with either a synthetic (Exosurf) or a modified natural (Survanta) surfactant. Using two-dimensional gel electrophoresis, SP-A in tracheal fluid obtained during the early and recovery phases of RDS exhibited lesser degrees of posttranslational modification than SP-A forms from control neonates. Administration of Exosurf or Survanta resulted in comparable increases in SPC in tracheal fluid. Preterm neonates with RDS seem to have an immature SP-A metabolism that persists for several days after birth. The type of surfactant used does not modify the recovery of SP-A or SPC in tracheal fluid from infants with RDS.