Background: Regular transfusion in thalassemia major patients increases life expectancy and improves quality of life. Blood transfusion is the main sources for viral transmission to Thalassemia patients. So, detection of viral antigens using more than one technique must be adopted. Iron and its binding proteins have immune regulatory properties and shifting of immune regulatory balance by iron excess or deficiency may produce severe deleterious physiological effects. Thus, the aim of this study was to assess the efficacy of immunization and determine the immune response of beta-thalassemia patients. Also, to evaluate the effects of iron overload chelating therapy and hepatitis B virus (HBV) vaccination on some immunological and hematological parameters in hepatitis and non hepatitis Egyptian thalassemia patients.               Methods:  Forty homozygote Thalassemia patients attending blood bank, therapeutic unite, Holding company for Biological production and Vaccine, VACSERA were chosen for this study (age range 4-30years, mean 14 years, 18 females 46% and 22 males 54%). Results:  There was no significant correlation between HBs Ab level in control and non vaccinated groups that include Thalassemia, hepatitis, non hepatitis, either iron chelating therapy dependent or independent patients. In the same time, there was no significant correlation between Ab level in vaccinated control and Thalassemia groups. HbF and HbA2 % showed significant and highly significant increases respectively, in most of groups especially, Thalassemia, hepatitis and iron chelating independent, vaccinated or non vaccinated groups. While HbA may be present in small amount or completely absent. RBCs count, Hb%, Hematocrit and MCV values were decreased significantly in all patient's groups vaccinated or non vaccinated compared to control group, while MCH and MCHC were not changed in patient' groups compared to control group. Platelets count was increased significantly in most patient' groups (except non vaccinated, Thalassemia, hepatitis, iron chelating dependent) compared to control group. Also, WBCs count was increased significantly in most groups (except non vaccinated, Thalassemia, hepatitis or non hepatitis, iron chelating dependent or independent) in comparison with the control group. All patients (hepatitis, vaccinated or non vaccinated) had high significant increase in gamma globulins compared to control group. Conclusion: Hematological and immunological measurements for hepatitis Thalassemia patients are important to monitor and treat the disease.