The hypothesis that the in vivo function of Survanta (Beractant) can be improved by supplementation with synthetic surfactant peptides B and C was tested in a surfactant-deficient rat model. Full length surfactant protein-B (SP-B1-78) (B) and palmitoylated surfactant protein-C (SP-C1-35) (C), and synthetic KL4 peptide were added to Survanta after extraction, creating extracted Survanta (ES) with 1% B, 2% B, and 2% B plus 1% C, or mixed with Survanta without extraction, creating modified Survanta (S) with 2% B, 2% B plus 1% C, and 2% KL4. Adult rats were ventilated with 100% oxygen, tidal volumes (VT) of 7.5 ml/kg and a rate of 60/min, and were lavaged until the PaO2 dropped below 80 mm Hg, when 100 mg/kg of surfactant was instilled. After 15 to 60 min of ventilation, pressure-volume (P-V) curves were generated in situ. Instillation of ES or S with 2% B plus 1% C led to the greatest increase in oxygenation, closely followed by ES and S with 2% B, and more distantly by S plus 2% KL4. TLC was comparable among the ES and S groups, but greater than that of air-placebo controls. These data suggest that spiking of Survanta with synthetic SP-B and SP-C increased oxygenation more effectively than B or KL4 alone in this surfactant-deficient rat model.