The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty-four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti-IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common. 