This study was performed to elucidate the mechanism of improved oxygenation after surfactant replacement therapy in respiratory distress syndrome (RDS) of the newborn infants. In 26 newborns with RDS, end tidal-CO₂ tension (PetCO₂), arterial blood gas analysis and pulmonary function tests were measured at baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in dead space/tidal volume ratio (V_D/V_T ratio=(PaCO₂-PetCO₂)/PaCO₂), oxygenation index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO₂) were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A-a)DO₂ improved, and V_D/V_T ratio decreased progressively after surfactant administration, becoming significantly different from the baseline at 30 min and thereafter with administration of surfactant. Pulmonary mechanics did not change significantly during the observation period. V_D/V_T ratio showed close correlation with OI and (A-a)DO₂, but not with pulmonary mechanics. These results suggest that decreased physiologic dead space resulting from the recruitment of atelectatic alveoli rather than improvement in pulmonary mechanics is primarily responsible for the improved oxygenation after surfactant therapy in the RDS of newborn.