Macrophages express distinct plasma membrane receptors for different isotypes of immunoglobulin, bear at least two receptors for cleaved third complement component (CR1 and CR3) and have a lectin-like receptor that mediates endocytosis of glycoproteins or glycoconjugates with terminal mannose or fucose residues (MFR). Interferon-gamma, a macrophage-activating factor, induces effects common to other interferons as well as having unique effects on cell function. The down-regulation of MFR, induction of IgG2a Fc receptors and Class II antigens and enhanced production of superoxide and hydrogen peroxide can be considered interferon-gamma-specific effects on macrophages. Previous reports described synergism of various interferon preparations in anticellular and antiviral effects. However, interferon-alpha/beta can selectively antagonize the down-regulation of macrophage MFR by interferon-gamma. The macrophage MFR and CR3 also play a synergistic role in the uptake of zymosan and Leishmania donovani in the absence of serum. The receptors may act independently or in concert. Cleaved third complement components can be specifically eluted from zymosan particles in the absence of exogenous complement and are derived from the macrophages themselves. These studies indicate a role for macrophage complement in local opsonization of pathogens at extravascular sites and focus on the role of the tissue macrophage in first-line host defence.