We have tested two surfactant preparations with the same phospholipid (PL) composition, containing recombinant surfactant protein-C (rSP-C surfactant) and without SP-C (plain PL surfactant). The effects of rSP-C surfactant were compared with the bovine-derived surfactant preparations Alveofact, bLES, and Infasurf in a lung lavage model, with surfactant given 1 h after the last lavage. The effects of surfactant treatment on histopathologic changes (e.g., hyaline-membrane formation) and improvement of oxygenation were compared with changes in untreated controls. The surfactants were given in doses of 25, 50, and 100 mg PL/kg body weight. At 120 min after treatment, only the protein-containing surfactants showed a statistically significant increasing dose dependence with respect to improving oxygenation. The values were 318 +/- 120 mm Hg, 443 +/- 58 mm Hg, and 480 +/- 43 mm Hg (mean +/- SD) for the three doses of rSP-C surfactant and 105 +/- 81 mm Hg, 100 +/- 69 mm Hg, and 131 +/- 108 mm Hg for the three doses of PL surfactant. The respective values for Alveofact were 104 +/- 81 mm Hg, 105 +/- 93 mm Hg, and 260 +/- 143 mm Hg; for bLES 373 +/- 138 mm Hg, 441 +/- 88 mm Hg, and 467 +/- 43 mm Hg; and for Infasurf 146 +/- 96 mm Hg, 284 +/- 178 mm Hg, and 436 +/- 70 mm Hg. The oxygen values of controls remained low, at 74 +/- 46 mm Hg. Only the protein-containing surfactants dose-dependently inhibited the formation of hyaline membranes. We conclude that rSP-C surfactant is at least as effective as bovine-derived surfactants. Furthermore, the data imply that the difference between plain PL surfactant preparations and bovine-derived surfactant preparations containing both SP-B and SP-C can be overcome by addition of SP-C.