Alloantibodies to high-frequency red cell antigens, defined as inherited traits occurring in 92% to 99% or more of the general population, are recognized as a cause of hemolytic transfusion reactions in humans. Here we describe a dog (dog erythrocyte antigen [DEA] 1.2- and DEA 4-positive) sensitized by prior blood transfusion, for which a compatible blood donor could not be found; transfusion of DEA 1.1-negative blood resulted in hemolytic transfusion reactions. Patient serum from days 1 (before first transfusion) and 16 was available for further testing; using 4 dogs with different blood types as potential donors, the major crossmatches were compatible using serum from day 1. However the crossmatches were all incompatible with serum from day 16, indicating that the patient was sensitized to an antigen after the first transfusion. The presence of an alloantibody against DEA 1.1 was not ruled out in this patient, but the incompatibility reactions of patient serum with red cells from donors negative for DEA 1.1 indicated that an alloantibody against a red cell antigen other than DEA 1.1 or any other known DEA for which typing reagents were available (DEA 3, 5, and 7) was present. Subsequently, red cells from 1 of the patient's siblings (DEA 1.2-, 4-, and 7-positive) were found not to agglutinate when incubated with patient's serum from day 16, ruling out the presence of an anti-DEA 7 antibody, and suggesting that an alloantibody against a common red cell antigen missing in the patient and sibling was responsible for the blood incompatibility reactions.(ABSTRACT TRUNCATED AT 250 WORDS)