ICL670 is an orally active representative of a new class of tridentate iron chelator developed for the treatment of blood transfusion–dependent iron overload in chronic anemias. In this randomized, double‐blind study, patients with transfusion‐dependent β‐thalassemia received single oral doses of ICL670 ranging from 2.5 to 80 mg/kg to investigate its safety, tolerability, and pharmacokinetics and to obtain preliminary information on pharmacodynamic effects. ICL670 was well tolerated, and no safety problems occurred up to 80 mg/kg. A plasma half‐life of 11 to 19 hours was found for ICL670, supporting once‐daily oral administration. AUC_0–24h and C_max of ICL670 increased nearly proportionally with the dose. The urinary excretion of ICL670 and its iron complex was less than 0.1% of the dose, and this was in accordance with the expected predominant iron fecal excretion induced by ICL670 (based on preclinical experiments). Notwithstanding, a positive trend toward increased amounts of urinary excreted iron was observed when the AUC_{0–24 h} of ICL670 and the iron complex exceeded specific threshold values at the 40‐ and 80‐mg/kg dose levels.