The phagocytic recognition by peritoneal macrophages plated on glass- or plastic-bound immune complexes of bovine plasma albumin (BSA) and anti-BSA was examined. Ingestion but not the attachment of erythrocytes opsonized with an IgG rich antiserum (EA) was markedly inhibited. In contrast, macrophage interactions with complement-coated (EAC) red cells, or ingestion of latex particles, yeast cell walls or glutaraldehyde-treated erythrocytes was not inhibited. Complexes prepared with pepsin-treated anti-BSA IgG were ineffective indicating a requirement for the Fc region. Inhibition of ingestion of EA was not a consequence of macrophage spreading and did not appear to be mediated by solubilized complexes or by cell-derived inhibitors of phagocytosis. Significant restoration of the ability to ingest EA was obtained when macrophages on complex-coated substrates were incubated for 4-8 h in medium enriched with mouse or fetal bovine serum. Restoration was also attained by removing macrophages from complex-coated dishes and replating onto uncoated dishes. The selective inhibition of ingestion of EA may be due to blocking of Fc receptors by the complexes but depletion of receptors by endocytosis of complexes cannot be ruled out. Alternatively, the complexes may have induced selective failure of the interiorization mechanism.