Recent data suggest that pulmonary macrophages may be heterogeneous. Several studies have demonstrated that alveolar macrophages are functionally and biochemically heterogeneous. In addition, interstitial macrophages, which are believed to be the precursors to alveolar macrophages, have been suggested to be heterogeneous. Therefore, this study was undertaken to determine if density-defined interstitial macrophages (DD-IM) are heterogeneous with respect to receptors for zymosan, immunoglobulin, and complement as well as morphologically. Furthermore, avidity for IgG was defined by opsonizing sheep red blood cells (SRBC) with different amounts of IgG. Interstitial macrophages were harvested and separated into 18 DD-IM subpopulations by centrifugation through a continuous iso-osmotic gradient of colloidal silica. Interstitial macrophages showed marked heterogeneity in cellular volume. Furthermore, macrophages of density 1.046 to 1.075 g/ml exhibited higher receptor activity capability of attaching and phagocytizing SRBC opsonized with small amounts of IgG and towards zymosan. All DD-IM exhibited similar abilities to attach complement-coated SRBC. These results demonstrate the functional heterogeneity of interstitial macropages with respect to IgG and zymosan.