The effect of intratracheal surfactant administration was studied in rats with adult respiratory distress syndrome associated with infection with nebulized Sendai virus. Thirty-six hours after infection, animals (n = 7) showed severely impaired gas exchange and acidosis during artificial ventilation (PaO2 = 152.2 +/- 18.7, PaCO2 = 65.3 +/- 19.2, pH = 7.26 +/- 0.11) with a pressure-controlled mode, standard frequency of 35/min, peak airway pressure of 15 cm H2O (15/0), inspiratory/expiratory ratio of 1:2, and F1O2 = 1. Gas exchange improved (P = 0.02) with increased ventilator pressures with PEEP (25/4). Forty-eight hours after infection, blood gas tensions could no longer be significantly improved by these same ventilator settings (PaO2 = 123.8 +/- 31.0, PaCO2 = 95.1 +/- 43.6, pH = 7.12 +/- 0.16, n = 9). At this time, surfactant replacement dramatically increased arterial oxygenation within 5 min (PaO2 = 389.4 +/- 79.9) and resulted in a fourfold increase in PaO2 within 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of respiratory failure during adult respiratory distress syndrome associated with viral pneumonia.