Effects of the development of Fe deficiency on changes in Fe and Zn metabolism and its possible interactions with dietary Zn were determined. Adequate (25 microg/g) and marginally deficient (5 microg/g) Zn diets containing a sufficient (40 microg/g) dietary Fe levels were fed for 2 wk. Thereafter, both dietary Zn groups were fed an Fe-deficient (2.2 microg/g) diet for 4 wk. It was found that the effects of an Fe-deficient diet began to occur 7 and 14 d after feeding the Fe-deficient diet. At this time, tissue Fe concentrations were depleted and rats were unable to maintain hemoglobin levels. The Fe-deficient diet also induced an immediate fall in plasma Fe concentration, transferrin saturation, and apparent Fe absorption, while the concentrations of liver cytochrome c increased as Fe deficiency developed. Decreases in liver and spleen Fe levels, as well as the activities of blood and bone marrow aminolevulinic acid dehydratase (ALA-D, EC 4.2.1.24) were observed 3, 7, and 14 d after feeding the Fe-deficient diet, and thereafter they were increased. On the other hand, the activity of plasma alkaline phosphatase (ALK-P, EC 3.1.3.1) decreased continuously as Fe deficiency progressed. With severe development of Fe deficiency, rats fed the Zn-adequate diet had increased levels of Zn concentration in the plasma, liver, spleen, kidney, and femur, whereas apparent Zn absorption was decreased. The decrease in apparent Zn absorption and the increase in tissue Zn concentration of rats might be related to the lowered Zn requirement, which is associated with the depressed Zn metabolism caused by feeding Fe-deficient diets.