A 37-year-old man with blood type O Rh-negative displayed a sudden, transient occurrence of an anti-D antibody shortly after receiving only type O Rh-negative packed red blood cells and Rh-positive random donor platelets. Testing of the blood products that were transfused demonstrated a high anti-D antibody titer in one of the packed red blood cell units that the patient received one day before the antibody was detected. Passively acquired antibodies should be routinely considered when evaluating the sudden occurrence of a positive indirect or direct antiglobulin test (Coombs' test) in a patient. Early recognition of this phenomenon will prevent unnecessary delays or inappropriate therapy.