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The relative contribution of transfusions of adult blood to the development of retrolental fibroplasia (RLF) in very low-birth-weight infants was examined. Five years of experience with the expanded use of replacement and exchange transfusions in 90 infants with birth weight less than or equal to 1,250 gm was reviewed. Twenty percent of the infants developed cicatricial RLF. Exchange transfusion was not related to development of cicatricial RLF. The incidence of RLF in infants receiving greater or equal to 130 ml of packed red blood cells per kilogram of birth weight as replacement blood transfusion (RBT) was significantly higher (42.9%) than that in infants receiving 61 to 131 ml of packed red blood cells per kilogram (15.4%) and infants receiving less than or equal to 60 ml of packed red blood cells per kilogram (0%), P less than .001. The need for RBT, however, was strongly correlated (r = .85, P less than .001) with increasing duration of O2 therapy. When O2 therapy was controlled for, the association between RBT and RLF did not achieve statistical significance (P = .07). The association between RBT and RLF remained significant when adjusted for duration of therapy in fractional inspired oxygen (FIO2) greater than 0.4. Further detailed studies of large numbers of susceptible infants are warranted to assess the magnitude of the contribution of transfusions of adult blood to development of RLF.