Fourteen studies were carried out on nine neonates who required assisted ventilation for the management of the respiratory distress syndrome. The object was to investigate the possibility that the inspiratory gas flow rate and the ratio of inspiration to expiration might influence the arterial oxygen tension. From the results it is concluded that both are crucial to optimal gas exchange, particularly in regard to oxygen. In this series failure to raise the arterial oxygenation above 50 mm Hg with assisted ventilation usually indicated a grave prognosis. Optimal inspiratory flow rates in terms of oxygenation were specific and reproducible for a given patient at a given time, but were variable during the course of the disease and could only be arrived at by empirical testing. A prolonged expiration phase was found more likely to provide better oxygenation. The presence of unequal regional pulmonary time-constants may explain variation in inspiratory flow rates and the ratio of inspiration to expiration found to produce optimal improvement in arterial oxygen tension.