A case of hyperhemolysis in a 2-year-old boy with β thalassemia major was noted. After several transfusions, he developed hyperhemolysis with a positive (C3d only) direct antiglobulin test (DAT) and no clinically significant RBC allo- or auto-antibodies. (There was a weak cold antibody, showing a narrow thermal range). Because there was no significant improvement with steroid and immunoglobulin infusions, cyclophosphamide therapy was tried with notable success.