The effect of an exchange transfusion on antioxidants in the plasma of newborns with rhesus hemolytic disease was studied. The antioxidant concentrations in donor blood were similar to normal adult values except for the lower vitamin C concentrations. Exchange transfusion decreased the newborns' iron and ferritin levels and increased their ceruloplasmin and transferrin (primary antioxidants) concentrations and latent iron-binding capacity. The changes in secondary antioxidant concentrations were variable; uric acid and thiols were stable, vitamin C and bilirubin fell, and vitamin E rose. The total peroxyl-radical trapping capacity of the secondary antioxidants did not change significantly. The fall in levels of thiobarbituric acid reactive substances, an index of lipid peroxidation, was related to the lower levels present in the donor blood. Exchange transfusion rapidly produced variable changes in the concentrations of prooxidant and antioxidant substances in plasma and may thus influence free radical metabolism in the newborn.