Background: Iron stores in the body are thought to be regulated by a mechanism associated with the rate of iron absorption from the diet, with no significant role played by iron excretion. We report the existence of an iron excretory process that results in the loss of significant amounts of liver iron.Methods and Results: Rats were fed 3% carbonyl iron for 9 weeks, which resulted in a 20-fold increase in liver non-haem iron. When the rats on this iron-loaded diet were switched to a low iron diet for 2 and 7 days, liver non-haem iron levels fell 30% and 45%, respectively. A similar fall in transferrin-bound plasma iron was also seen. As the liver iron had not redistributed to other body compartments, it was concluded that the iron had been excreted and that the excreted iron represented a loss of 22% and 28% in total body non-haem iron over 2 and 7 days, respectively. Ligation of the common bile duct in iron loaded rats that had been switched to the iron-deficient diet was accompanied by a similar loss of liver iron and also hepatocellular damage. In addition, measurement of enterocyte iron levels showed that only approximately 5% of the total iron excreted was found in these cells.Conclusion: Neither bile nor enterocytes play a significant role in iron excretion. The similarity in the degree of fall in transferrin-bound iron levels with a change in diet suggests that iron excretion involves the uptake and excretion of transferrin bound-iron, possibly by goblet cells. The observed hypertrophy of the intestinal mucosa associated with carbonyl iron feeding may facilitate hypersecretion of mucous and the excretion of this iron. (C) 2000 Blackwell Science Asia Pty Ltd.