PURPOSE: The purpose of this study was to assess the usefulness of mean corpuscular volume (MCV), red cell distribution width (RDW) and hemoglobin distribution width (HDW), which can be measured easily with automatic blood cell counter, in differentiating anemia of acute infection from iron deficiency anemia (IDA) in the early phase of infection. We also wanted to determine whether decreased erythropoietin (EPO) production contribute to the pathogenesis of anemia of acute infection. METHODS: 39 anemic children who were admitted to Kangbuk Samsung Hospital due to acute infectious disease between June 1997 and September 1998 were studied. We measured serum ferritin level by radioimmunoassay and divided the patients into two groups according to the serum ferritin level. The children with serum ferritin level above 30 ng/mL were included in anemia of infection group, and the children with serum ferritin level under 10 ng/mL were included in IDA group. Anemic children whose ferritin level were between 10 ng/mL and 30 ng/mL were excluded. We measured MCV, RDW and HDW by automatic blood cell counter and compared them between two groups. We also measured EPO concentration in anemia of acute infection group and compared with that of the control group. RESULTS: 1) Most common acute infectious disease accompanied by anemia of acute infection were acute gastroenteritis, acute pharyngitis, and pneumonia. 2) Complete blood count (CBC) revealed normocytic normochromia in anemia of acute infection and microcytic hypochromia in IDA. MCV of IDA group was significantly lower than that of anemia of acute infection group (65.2+/-8.7 fL vs 82.4+/-5.5 fL, P<0.005). RDW in IDA group was significantly higher than that of anemia of acute infection group (17.1+/-2.5% vs 15.0+/-1.0%, P<0.005). HDW in IDA group was significantly higher than that of anemia of acute infection group (3.2+/-0.5 g/dL vs 2.4+/-0.2 g/dL, P<0.005). 3) The mean EPO concentration in anemia of acute infection group was significantly higher than that of control group (27.1+/-14.5 mU/mL vs 18.4+/-8.7 mU/mL, P<0.05). CONCLUSION: 1) We concluded that MCV, RDW and HDW are effective parameters to differentiate anemia of acute infection from IDA. 2) Decreased EPO production may have less significant role in the pathogenesis of anemia of acute infection compared to anemia of chronic disease. 3) Our results suggested that other factors such as accelerated erythrocyte destruction or hypoferremia may contribute to the development of anemia of acute infection. Further studies will be required to identify the pathophysiology of anemia of acute infection.