The delivery of iron into cells is mediated by transferrin via its receptors that reside on the cell surface. To clarify the role of reticuloendothelial cells in iron metabolism, the distribution of transferrin receptors on macrophages in various organs and on peripheral blood monocytes was examined by scanning electron microscopy and radiobinding assay. Radiobinding assay of human alveolar macrophages revealed the presence of 19.88±8.19×10(4) diferric trabsferrin receptors per cell (mean±SD) and a binding constant of 4.42±3.41×10(8)M(-1). Human peritoneal macrophages and macrophages in the thoracic cavity had fewer diferric transferrin receptors (2.68×10(4), 8.10×10(4), 4.3×10(3) and 2.1×10(4) receptors/cell). Peripheral blood monocytes had no diferric transferrin receptors. Diferric transferrin receptors were also found on guinea pig alveolar macrophages (2.25±0.78×10(4)) and peritoneal macrophages (1.6±0.2×10(3)), while they were absent on rat alveolar and peritoneal macro-phages. Scanning electron microscopic findings in guinea pig alveolar macrophages revealed a patch-formed distribution of apotransferrin receptors and diferric transferrin receptors on the characteristic ruffle-covered surface of macrophages. The number of transferrin rece-ptors varied among individual cells even within the same species or same organs. These findings suggest that the macrophages with transferrin receptors in various organs of human and guinea pigs are heterogeneous among different species and cells, and have different functions in iron metabolism.