OBJECTIVE To study the clinical significance of the serum transferrin receptor (sTfR) and ferritin in distinguishing between iron deficiency anemia (IDA), anemia of chronic disease (ACD) and ACD with complicating IDA (ACD-IDA). METHODS One hundred and thirteen subjects enrolled into the study were divided into four groups including 28 health volunteers as control, 29 patients with IDA, 27 patients with ACD (sTfR level <or= 20.0 nmol/L, ACD1 group) and 29 patients with ACD-IDA (sTfR level > 20.0 nmol/L, ACD2 group). sTfR, serum ferritin (SF), serum iron (SI), total iron-binding capacity (TIBC), transferring saturation (TS) and complete blood count were measured in all the enrolled subjects or patients. Bone marrow iron stain was examined in 10 cases of ACD1 and 16 cases of ADC2. RESULTS In IDA group, MCV (68.0 +/- 11.3) fl was the smallest; SI, TS and SF were significantly decreased but sTfR level was increased as compared with the control group (SI) (19.6 +/- 10.1) mg/L vs (81.7 +/- 30.6) mg/L, TS (5.5 +/- 2.3)% vs (27.0 +/- 12.0)%, SF (4.3 +/- 2.8) micro g/L vs (43.3 +/- 26.8) micro g/L and sTfR (67.2 +/- 40.3) nmol/L vs (15.6 +/- 4.1) nmol/L (P <or= 0.01). SI (60.7 +/- 28.7) mg/L, and TS (21.1 +/- 9.8)% were not different statistically (P > 0.05) but SF (627.3 +/- 40.3) micro g/L level was increased in ACD1 group as compared with the control group (P < 0.01). Bone marrow iron stain showed no iron deficiency in 10 cases of ACD1. In ACD2 group, SF (320.5 +/- 156.0) micro g/L level was higher than that of the control group, but lower than that of the ACD1 group (P <or= 0.01); bone marrow iron stain showed iron depletion in 14 of the 16 patients. CONCLUSIONS High sTfR level may reflect iron deficiency status of the body and is a more sensitive parameter to diagnose iron deficiency anemia. sTfR level is less influenced by chronic inflammation, and able to distinguish ACD from ACD-IDA.