The present study investigated the influence of preceding blood transfusions from randomly selected unrelated dogs on the outcome of marrow grafts between histoincompatible littermates. Two groups of recipients were conditioned for marrow grafting by 1,200 R of whole body irradiation followed within 4 hr by infusion of hemopoietic cells from the incompatible littermate. Group 1 consisted of 12 dogs not given a preceding blood transfusion. Group 2 was made up of 9 dogs given 3 transfusions on each of 3 occasions: 24, 17, and 10 days before grafting. All 12 dogs in group 1 showed prompt and sustained marrow engraftment. Six of nine dogs in group 2 showed acute marrow graft rejection and died with marrow hypoplasia. Three showed sustained hemopoietic engraftment. It was concluded that multiple prior transfusions from unrelated dogs in most instances immunized a recipient and prevented subsequent marrow engraftment from a histoincompatible littermate