We measured the in vivo oxygen saturation of hemoglobin in the arterial blood of 34 sick newborn infants with a new, rapidly responding, continuously recording, catheter oximeter. The oxygen saturation, SaO2, was found to fluctuate between 85 and 95% in infants with pulmonary disease who are in a stable condition and breathing spontaneously. Severe desaturation occurred during apnea and after procedures such as chest percussion and suctioning of the endotrachael tube. The effects of changes in respiratory therapy were quickly manifested by changes in SaO2. This was particularly useful in guiding resuscitation of newborn infants who were asphyxiated at birth. Blood sampling for measurement of PaO2 can be done less frequently, reducing the need for blood transfusions in small infants.