Serum transferrin receptors (TfR) are a sensitive index of tissue iron availability, increasing progressively in response to functional iron deficiency. Unlike conventional laboratory tests of iron status, serum TfR are unaffected by underlying acute or chronic infection. Therefore, serum TfR measurement is particularly promising for evaluation of iron status when iron deficiency is simultaneously present with overt or subclinical infection or inflammation--a scenario often seen in patients seeking medical care, in elderly persons, and in persons living in developing countries. This test is also promising for assessment of iron status in pregnancy because it is not confounded by gestational effects. With the exception of conditions associated with markedly enhanced erythropoiesis which can increase TfR independently (e.g., megaloblastic anemia, thalassemia), serum TfR determination is a specific test of iron status. Serum TfR measurement is also reliable; a single, small amount of blood sample is adequate for its accurate determination. These sensitivity, specificity, and reliability characteristics of serum TfR measurement enable it to enhance confidence in iron status assessment in complex situations with the standard repertoire of laboratory tests.