Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty-two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen-untyped blood after 8 to 28 units of antigen-negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti-recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO-unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program.The Blood Bank plays an important role in the supportive care of liver transplant patients before, during, and after surgery. Before transplant for end-stage liver disease, patients are often transfused for bleeding due to portal hypertension, esophageal varices, deficient coagulation factors, thrombocytopenia, or other surgery. After transplant, many patients need further transfusions and some require retransplantation. The liver transplant program at the University of Pittsburgh has the world's largest such experience, and since the program's inception in 1981, its overall perioperative and postoperative blood use has been carefully documented.1 -5 These patients have ample opportunity for red cell (RBC) alloimmunization.The purpose of this study was to examine all RBC antibody problems encountered in 1000 consecutive liver transplants performed in our center from February 1981 to February 1987. Previously, as part of an examination of the relationship of the HLA system to RBC alloimmunization, 6 we reported a 9.5 percent frequency of potentially significant RBC alloantibodies in 263 adults. We present here our cumulative experience in both adults and children with regard to 1) the overall frequencies of RBC antibodies; 2) the onset and duration of significant RBC antibodies relative to transplant immunosuppression; 3) the cases in which insufficient compatible blood was available for surgery; and 4) the frequencies and causes of © J. B. Lippincott Co.