We have used the ability of opsonized bacteria to stimulate luminol-enhanced chemiluminescence (CL) of human polymorphonuclear leukocytes (PMN) to examine the opsonic capabilities of commercially available human intravenous immunoglobulin (IVIG) preparations. The method was tested against 14 strains of drug-resistant gram-positive bacteria (including methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant S. aureus, vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae), and 23 strains of gram-negative bacteria (including extended-spectrum β-lactamase-producing bacteria, metallo-β-lactamase-producing bacteria, β-lactamase-negative ampicillin-resistant Haemophilus influenzae). An Fc-intact IVIG preparation treated with polyethylene glycol (PEG) was evaluated for opsonization effectiveness against these bacteria in vitro. The opsonization of these organisms was enhanced by an Fc-intact IVIG, and the opsonic activity was dose dependent. A pepsin-treated IVIG preparation exhibited poor opsonic activity for all bacteria tested. These results suggest that Fc-intact IVIG, which augments opsonic activity against various drug-resistant bacteria, will be a useful addition to the treatment of severe bacterial infections in immunocompromised patients with impaired serum opsonic capacity.