The bilirubin titration point--the lowest bilirubin concentration at which loosely bound bilirubin could be demonstrated by Sephadex gel filtration--was determined in samples collected before, during, and on completion of 17 exchange transfusions as well as in the discarded and donor blood. The bilirubin titration point expressed either as bilirubin concentration or as bilirubin/albumin molar ratio failed to be increased by the exchange transfusion and, in each case at the end of the procedure, the titration point was below the expected level, assuming that the donor albumin was going to retain its binding properties in the infant's circulation. The bilirubin titration point was also depressed in the discarded blood, and the depression was inversely related to the amount of bilirubin removed by the exchange transfusion (expressed as mg/kg of body weight/mg of initial bilirubin concentration). These results are interpreted as an indication that interfering substances are responsible for the decreased binding of bilirubin in newborn, particularly preterm, infants. In practical terms the criteria for a repeat exchange transfusion should be the same as for the initial one, as no change in the bilirubin binding properties of the serum is likely to occur following exchange transfusion.