Eighty multi-transfused beta-thalassemics--40 of them on regular transfusion (RT) (every 3-4 weeks) and 40 irregularly transfused (IT)-and 20 age- and-sex-matched controls were evaluated for serum erythropoietin (sEpo) and soluble serum transferrin receptors (sTfr) as indicators of erythropoietic activity. All subjects were studied for pre-transfusion hemoglobin (Hb), reticulocytic index (RI), serum ferritin, sEpo and sTfr. Results showed that the mean RI, sEpo and sTfr values were significantly higher in the IT group (2.8; 80 mU/ml; and 19 microg/ml, respectively) compared to the RT group (1.2; 35.2 mU/ml; and 13.9 microg/ml, respectively) and controls (1.1; 22.6 mU/ml; and 7 microg/ml, respectively) (p < 0.05); while only the mean sTfr value was significantly higher in the RT group compared to controls. The mean pre-transfusion Hb was significantly lower in the IT group (8 g/dl) compared to both the RT group (9.3 g/dl) and controls (12.5 g/dl) (p < 0.05); while the RT group level was significantly lower than controls. There was an inverse correlation between Hb level on one hand and sEpo (r = 0.324,p < 0.05), sTfr (r = -0.651, p < 0.05) and RI (r = -0.451, p < 0.05) on the other. In summary, sEpo, sTfr and RI could be used as accurate and reliable indicators of successful erythroid marrow suppression and for the determination of optimal pre-transfusion Hb level in thalassemia on an individual basis, with sTfr being the most sensitive indicator.