In a prospective observational study of preterm infants less than 29 weeks gestation (part of the prematurity and respiratory outcomes project, PROP), infants who were either on supplemental oxygen or room air through a nasal cannula were subjected to a physiological challenge test. The oxygen or airflow was steadily decreased under close monitoring of oxygen saturation and the respiratory pattern. Of 49 infants tested, nearly one-fourth passed the challenge test. Among the infants who failed the test, around 40% also had marked increases in periodic breathing. These infants presumably had unstable control of breathing that contributed to oxygen requirement at 36 weeks postmenstrual age, and was unmasked during the physiological challenge.