The transmembrane protein, transferrin receptor (TfR), exists in serum as a soluble form that lacks cytoplasmic and transmembrane domains (residues 1-100). The level of soluble TfR in serum is a sensitive indicator of total erythropoiesis and iron deficiency. This study revealed that the major part of soluble TfR was saturated by transferrin (Tf) in serum, forming a stable complex which was more immunoreactive than intact TfR. Thus, we proposed that serum soluble TfR should be measured as the TfR-Tf complex (TRC), using prepared TRC for assay standardization. We developed a new assay for TRC, employing antibody-coated latex agglutination nephelometry (LA). Rapid and reproducible measurements were achieved using an automated analyzer. The values obtained by this LA assay were closely correlated with those obtained by conventional enzyme immunoassay (r = 0.967). The mean level of TRC in 179 adult healthy subjects was 1.62 mg/l. Patients with iron-deficient anemia showed significantly higher TRC levels than the healthy subjects.