The endogenous production of carbon monoxide ( V(CO)) in newborn infants was measured by serial determinations of blood carboxyhemoglobin during rebreathing in a closed system. Mean V(CO) in nine full-term infants was 13.7 +/-3.6 mul CO/kg per hr (SD), and in four erythroblastotic infants V(CO) ranged from 37 to 154 mul CO/kg per hr preceding exchange transfusion. Mean red cell life-span (MLS) and total bilirubin production were calculated from V(CO). MLS in normal newborns was 88 +/-15 days (SD), and bilirubin production was 8.5 +/-2.3 mg/kg per 24 hr. This is more than twice the amount of bilirubin normally produced in the adult per kilogram of body weight. Normal infants achieved a net excretion of bilirubin of at least 5.6 +/-2.3 mg/kg per 24 hr (SD) as calculated from the bilirubin production and the measured rise in serum bilirubin concentration.The measurement of V(CO) should prove valuable in the study of red blood cell survival and bilirubin metabolism in the newborn infant.