BACKGROUND Serum transferrin receptor (sTfR) concentration has been recognized as a reliable laboratory indicator of iron deficiency in recent years. But its response to iron supplementation has not been investigated. METHODS We evaluated the sTfR concentrations in 15 patients diagnosed with iron-deficiency anemia, in 30 patients receiving maintenance hemodialysis (HD) with iron repletion and in 31 healthy controls. The serial changes of sTfR concentration and their correlation with serum ferritin in patients with iron deficiency under iron repletion were also examined in three patients. RESULTS In patients with iron-deficiency anemia, the sTfR concentration was 5.6 +/- 2.4 mg/ml, significantly higher than that in the control group (1.8 +/- 0.4 mg/ml) and patients receiving maintenance HD with iron repletion (1.7 +/- 0.5 mg/ml). The three patients with iron-deficiency anemia who received eight to 16 weeks of iron supplementation showed steady and significant decreases in sTfR concentration and significant increases in serum ferritin and transferrin saturation. However, the decreases in sTfR concentration did not occur immediately, as did the increases in serum ferritin and transferrin saturation, following iron repletion. There was a four-week delayed response in the decrease of sTfR concentrations as measured against serum ferritin and transferrin saturation. CONCLUSIONS sTfR concentration may not be as effective as an early index of iron repletion compared with serum ferritin and transferrin saturation.