An acute hemolytic transfusion reaction resulting from dog erythrocyte antigen (DEA) 1.1 incompatibility developed in a dog previously sensitized to DEA 1.1 by a transfusion 3 years earlier. The dog developed fever, pigmenturia, and lethargy, and its PCV did not rise as expected. The donor blood was type DEA 1.1 positive, whereas the recipient's blood was type DEA 1.1, DEA 1.2, and DEA 7 negative. A major crossmatch was later found to be strongly incompatible. Studies of the recipient's plasma revealed a specific anti-DEA 1.1 alloantibody of the IgG class with high hemolysin and agglutinin activity. Such acute hemolytic transfusion reactions can be avoided by crossmatching previously transfused dogs and by using dogs that are type DEA 1.1 negative (and preferably also type DEA 1.2 and DEA 7 negative) as blood donors.