The international committee on chelation (ICOC) of deferiprone (L1) and deferoxamine (DFO) combination therapy was the first protocol reported to have achieved normal range body iron store levels (NRBISL) in β-thalassemia major (β-TM) patients. A follow-up study in eight β-TM patients has been designed to investigate the factors affecting the rate of iron removal leading to NRBISL. The patients had variable serum ferritin [mean ± SE (standard error) =1692 ± 366, range 539-3845 μg/L)] and magnetic resonance imaging (MRI) T2* relaxation times cardiac (mean ± SE =11.1 ± 2.5, range 4.5-24.2 ms) and liver (mean ± SE = 4.3 ± 1.8, range 1.4-14 ms). Organ function, blood and other biochemical parameters were regularly monitored for toxicity. The ICOC L1 (80-100 mg/kg/day) and DFO (40-60 mg/kg, at least 3 days per week) combination therapy caused an increase in cardiac (mean ± SE =30.2 ± 2.3, range 22-41 ms) and liver (mean ± SE =27.6 ± 2.8, range 9.1-35 ms) T2* and reduction in serum ferritin (mean ± SE = 158 ± 49, range 40-421 μg/L) to within the NRBISL. The rate of normalization was variable and in one case was achieved within 9 months, whereas the longest was about 3 years. The initial iron load, the rate of transfusions, the combination dose protocol and the level of compliance were the major factors affecting the rate of normalization of the iron stores. No serious toxicity was observed during the study period, which lasted a total of 24.7 patient years.