An in vitro model system was used to investigate how human monocytes recognize influenza A/WSN(H1N1)-infected epithelial cells, and the role that anti-influenza IgA and IgG Abs play in this interaction. Pretreatment of the monocytes with neuraminidase or F(ab')2 fragments of a mAb against the Ca1 epitope on the hemagglutinin (HA) molecule inhibited monocyte adherence to the infected cells. This suggested that monocytes bound to the sialic acid binding site on the HA molecule and not to other viral or epithelial cell Ags. In the presence of neutralizing concentrations of intact Abs (human serum IgA, secretory IgA, IgG, or mouse anti-HA mAb), monocytes were unable to bind to influenza-infected epithelium or to phagocytize the IgA or IgG immune complexes formed with influenza virus, even though they could use these same Abs to attach to or phagocytize inert particles. Under conditions of Ag excess and low concentrations of Ab, monocytes bound primarily to the viral HA molecule, but showed some recognition of the viral immune complexes. This dual binding did not increase monocyte adherence to the infected epithelium above that observed with virus alone. These findings indicate that neutralizing concentrations of IgA or IgG Abs, the predominant Abs found in the upper and lower respiratory tract, respectively, do not augment and can prevent monocyte recognition of influenza virus. This suggests that in vivo monocytes must use a non-Fc-mediated mechanism to adhere to and phagocytize these immune complexes.