In general, naturally occurring cold autoagglutinins react optimally at low temperatures. We describe a young child who experienced an acute hemolytic transfusion reaction by an unusual autoanti-I. The IgM autoanti-I was detected at 4°C (titer 256) and also reacted at 30°C. This case highlights the potential hazard of transfusing units of blood immediately upon removal from the blood refrigerator, especially into neonates and children of small stature.