A protocol for transfusion of infants with erythrocyte T-antigen activation was evaluated for safety and effectiveness in a prospective, 3-year, sequential series of 1672 infants admitted for intensive care. Erythrocyte T antigens are activated by enzymes produced by clostridia or other bacteria in infants with sepsis, often in association with necrotizing enterocolitis. Transfusion of these infants with blood products containing plasma carries the risk of causing intravascular hemolysis. Our transfusion protocol included testing for T-antigen activation, restricting transfusion of patients with activated T antigens to washed erythrocytes or washed platelets whenever possible, and selecting donors with low-titer anti-T when plasma-containing blood products were required. In this series, 10 patients had T-antigen activation, including four with clostridial infections. Severe hemolysis occurred in one patient who received plasma before T-antigen activation developed. Of five patients who received low-titer anti-T plasma, mild hemolysis occurred in three and no hemolysis in two. Four patients who received no plasma-containing blood products experienced no hemolysis. Used cautiously, this protocol allows a full range of transfusion therapy to infants with T-antigen activation.