Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P(A-a)O2 pulmonary compliance (CL), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured CL by pneumotachography and esophageal manometry and FRC by helium dilution. Mean (+/- SEM) values for CL and FRC increased (CL from 0.28 +/- 0.02 to 0.35 +/- 0.03 mL/cmH2O)/kg and FRC from 18.6 +/- 1.4 to 22.2 +/- 1.1 mL/kg; P < 0.05), and P(A-a)O2 and the oxygenation index (OI) decreased (200 +/- 19 to 169 +/- 14 mm Hg and 6.9 +/- 0.44 to 5.4 +/- 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy.