The optimal range of pulse oximeter oxygen saturation (SaO2) for infants with chronic lung disease (CLD) has not been well established. We quantified episodes of spontaneous desaturation, at two different ranges of SaO2. For 1 hr each, we alternatively administered inspired O2 concentrations (FiO2) necessary to maintain an SaO2 of 94-96% or 87-91% to 21 patients (mean birth weight, 865 g; gestational age, 27.3 weeks; postnatal age 40.6 days) with CLD (defined by FiO2 > 0.21 at > or = 28 days and radiographic evidence). SaO2 was monitored with the Nellcor N-200 oximeter and analyzed by a computer program (SatMaster). The percentage of time the infants desaturated to levels of SaO2 < 85 and < 80% revealed significantly fewer spontaneous episodes during the hour of higher baseline SaO2 (P < 0.0002). Comparison of episodes of spontaneous desaturation to SaO2 < 80 and < 85%, lasting 0-15, 16-30, 31-45 sec also showed significant differences between the two levels of SaO2. We conclude that when infants with CLD are maintained at a higher SaO2 they probably experience fewer episodes of spontaneous desaturations, because of less alveolar hypoxia. We believe that attempts at weaning the FiO2 should be tempered with the need of maintaining an adequate SaO2. Therefore, prolonged monitoring of oxygenation in infants with CLD at different levels of SaO2 could be helpful during the weaning process.