Twelve neonates with severe lung disease were studied while mechanically ventilated with volume pre-set infant ventilators, using different I:E ratios and different airway pressure waves. While FIO2 tidal volume, respiratory rate, and PEEP remained constant, I:E ratios were increased, first by reducing inspiratory flow rate, which produced a triangular pressure wave, and then by using an inspiratory time hold mechanism, which produced an inspiratory plateau or squared pressure wave. Peak inspiratory pressure, mean airway pressure, PaO2, PaCO2, pH, and blood pressure were measured and compared for each I:E ratio and pressure wave combination. In all patients, increases in oxygenation appeared to be directly related to increases in MAP. Optimum oxygenation and ventilation occurred with the I:E ratio and pressure wave combination that produced the highest MAP. Because MAP changes with any alteration in PEEP, I:E ratio, or airway pressure wave, it is a clinically useful composite measure of all pressures transmitted to the airways by a mechanical ventilator.