BACKGROUND: In diagnoses of iron deficiency anemia(IDA) and anemia of chronic disease(ACD), bone marrow examinations, the gold standard, are too invasive. Iron parameters such as serum ferritin, iron, and total iron binding capacity(TIBC), may be altered by perturbations as varied as infection, inflammation, and malignancy. Clinically, IDA may be the initial manifestation of an occult carcinoma of the gastrointestinal tract, thus noninvasive methods with high sensitivity are now required in detecting tissue iron deficiency. In this study, we investigated the diagnostic availability of the soluble transferrin receptor(sTfR) in differential diagnosis of IDA and ACD. SUBJECTS AND METHODS: Thirty eight patients with uncomplicated IDA(ferritin <12.0 microgram/L), 22 patients with uncomplicated anemia of chronic disease(ferritin > or =60.0 microgram/L), 7 patients with combined anemia(IDA+ACD, 12.0 microgram/L< OR = ferritin <60.0 microgram/L), and 20 normal controls were included in the study. The blood levels of sTfR, hemoglobin(Hb), RBC indices, serum ferritin, serum iron, and TIBC were measured and the transferrin saturation was calculated. The sTfR levels were compared with each other group. The correlations between iron parameters and the sTfR levels were investigated in each group. RESULTS: The sTfR receptor levels were significantly higher in uncomplicated IDA patients(56.2+/-19.8 nmol/L) than in normal controls(17.9+/-3.9 nmol/L) and uncomplicated ACD patients(15.3+/-7.5 nmol/L). No difference of the sTfR concentrations was observed between ACD patients and normal controls. In combined group, four of the 7 cases showed higher sTfR values than that of normal controls. Good inverse correlation was observed between Hb and sTfR levels in uncomplicated IDA group. There were no correlations between iron parameters and sTfR levels in the other groups. CONCLUSION: Because the sTfR level was not elevated in ACD and was significantly higher in IDA, blood determination of the sTfR levels may be a useful method in differential diagnosis of IDA and ACD. The sTfR is the most useful marker expressing the functional iron deficiency without being affected by chronic diseases. Because the sTfR levels were inversely correlated with Hb in IDA patients, the combined use of two parameters, ferritin and sTfR which are the indices of storage iron and functional iron respectively, may allow accurate definition of the entire range of body iron status.