Decorporation therapy is the only known effective method of reducing the radiation dose to persons following accidental internal contamination with transportable radionuclides. Deposits of actinides in bone should be minimized because development of osteosarcoma appears to be related to internal exposure. In contrast with other actinides, such as plutonium or americium where chelating agent treatment is efficient, the therapeuric approaches used for cases of uranium contamination are widely ineffective. This is the first report on in vivo efficacy of a chelating agent, a siderophore analogue code named 3,4,3-LIHOPO, after systematic exposure to natural uranium in the rat. Using the classical antidotal therapy (sodium bicarbonate) for comparison, this ligand has been investigated for its ability to remove uranium from rats after intravenous or intramuscular injection as nitrate. Following an immediate single intramuscular or intravenous injection of 3,4,3-LIHOPO (30 mumol.kg-1) urinary excretion of uranium was greatly enhanced with a corresponding reduction 24 h later in kidney and bone uranium content (to about 20 and 50% of the control rat respectively). Under identical experimental conditions, sodium bicarbonate (640 mumol.kg-1) reduced the uranium content in kidney in kidney and bone only to about 90 and 70% of controls respectively, and there was less enhancement of uranium excretion. However, when treatment was delayed by 30 min and administered intraperitoneally, there was no marked difference in retention and excretion of uranium between the two compounds. As this ligand showed no apparent irreversible toxicity at effective dosages, it is concluded that the administration of the 3,4,3-LIHOPO chelating agent represents potentially a most significant advance for prompt treatment of uranium contamination, while a more detailed investigation is necessary on the possible advantage when treatment delayed.