A retrospective study of pretransfusion testing records compared the utility of the antiglobulin test (AGT) phase of the crossmatch and the autologous control (autocontrol) for detecting clinically significant alloimmunization to red cells (RBCs). Of 110,780 consecutive crossmatches, 141 were positive after a negative antibody screening test; only 4 of these were due to alloantibodies of potential clinical significance, for a predictive value of a positive AGT crossmatch, after a negative antibody screen, of 2.8 percent (4/141). The frequency of potentially shortened RBC survival was 1 in 27,685 units crossmatched. During a similar period, 56,090 autocontrols were performed with the antibody screen. The autocontrol was positive on 902 samples in which the antibody screen was negative. Antibody identification performed in 684 cases generally yielded only cold or warm autoagglutinins. In 96 cases, some form of alloantibody was detected, but only 25 had potential clinical significance by our criteria. Eight of these alloantibodies had concurrently caused in vivo sensitization of RBCs and were classified as delayed hemolytic transfusion reactions. The predictive value of the autocontrol, calculated as the number of significant alloantibodies detected in autocontrol-positive, antibody-screen-negative samples, was 3.6 percent (25/684). Inspection of these cases revealed 11 in which shortened RBC survival might have resulted if the serologic abnormality had not been detected. Thus, the autocontrol had a slightly greater yield of clinically significant findings than the AGT crossmatch.(ABSTRACT TRUNCATED AT 250 WORDS)