Thalassemia is the world's most common hereditary disease; therefore, more interest has been devoted for the development of the screening procedure of this disease. In beta-thalassemia major, the subject of the current study, impaired biosynthesis of beta-globin leads to accumulation of unpaired alpha-globin chain. The objective of the present study, was to examine many of the biophysical properties of beta-thalassemia major red blood cells (RBCs) and to study the possibility of use of any of them as a preliminary screening tool for beta-thalassemia. The percentage of normal hemolysis, osmotic fragility test, turbidity test, rheological properties, and dielectric properties, were studied in 20 regularly blood transfused thalassemia major patients who were under chelation therapy and their status were compared with those of 10 healthy subjects. There was an increase in the percentage of hemolysis for beta-thalassemia by 114.6% compared to the normal RBCs. The fragility curve for beta-thalassemia RBCs showed a shift toward lower NaCl concentration compared to the normal curve. The average osmotic fragility (H(50): the NaCl concentration producing 50% homolysis) for beta-thalassemia was found to be 3.21 +/- 0.67 g/l, whereas for normal RBCs it was 5.5 +/- 0.31 g/l. The turbidity curve of the beta-thalassemic RBCs showed a shift toward higher detergent concentration of the normal curve, with higher value for the average membrane solubilization (S(50)). The viscosity value of whole blood beta-thalassemia was found to be 3.916 +/- 0.56 cp whereas for normal blood was 2.516 +/- 0.36 cp. The relative permittivity, dielectric loss, and AC conductivity of RBCs decreased significantly compared to normal samples. This could be attributed to the loss of the insulating properties of the membrane and loss of its surface charge of thalassemic RBCs. As can be noticed, several factors showed clear difference between thalassemic and normal blood samples. Some of these parameters could be measured immediately after sample withdrawal and require short time to perform the measurements. This offers the advantages of being effective, low cost, and fast techniques, therefore, we suggest that these techniques could be applied for beta-thalassemia major screening purposes.