beta-thalassemia is considered a severe, progressive anemia, which needs regular transfusions for life expectancy. One of the most important complications of regular blood transfusions may be alloimmunization, which increases the need for transfusion. This study was performed to investigate the production of red cell alloantibodies in beta-thalassemia patients in Shiraz, southern Iran. Blood sampling was performed among 711 beta-thalassemia patients in Dastgheib hospital in 2002-2004. Direct and indirect coombs tests were performed to check the auto and alloantibodies and a panel test was conducted to detect the type of alloantibodies. Auto and alloantibodies were observed among 1.7% and 5.3% of patients, respectively. The most common alloantibodies were Anti-kell (50%) > Anti-Rh (D) (15.8%) > Anti-Rh (E) (10.5%). All the patients who had developed alloantibody were in the age group of 6 years or more. So for decreasing the rate of alloantibody synthesis, we should crossmatched the packed cells for minor blood groups especially for kell and Rh(E) in addition to major blood groups from the start of transfusion.