This retrospective study of red cell antibodies covered the period from 1985 to 1993. A three-cell antibody screen, 22% albumin enhancement, and a polyspecific antiglobulin reagent assay were performed. From a total of 159,262 patients in the data set, 6996 antibodies were detected among the sera of 4700 patients (2.9%). Four thousand two hundred thirty-five (60.5%) alloantibodies of potential clinical significance were found. These included anti-K1 (23.0%), -E (17.6%), -D (12.4%), -Le(a) (7.3%), -C (6.3%), -Fya (5.7%), and -c (4.4%). Cold agglutinins were found in 1119 positive antibody screens, 261 had warm autoantibodies, and 554 had high-titered, low-avidity antibodies. Three hundred seven were clinically insignificant (eg, Sda and Bga). Five hundred seventeen were too weak to identify. Most patients' sera demonstrated only one antibody (69.3%), but there was a strong linear correlation between the total number of recorded red cell transfusions and the number of antibodies found (r = .976; P < .0001). There was a higher percentage of females with antibodies than the percentage of females in the total study population (59.2% versus 43.8%, P < .0001). Two hundred nine of 554 (37.7%) high-titered, low-avidity antibodies and 349 (31.2%) of 1119 of the cold agglutinins accompanied or obscured clinically significant antibodies.