Several standard intravenous immunoglobulin G (IVIG) products are available in the United States and have been used with the intent to treat or prevent infections in neonates. We evaluated more than 100 lots of IVIG, from 6 products, to determine the amount of opsonic antibody against neonatal pathogens. Neutrophilmediated opsonophagocytosis was used to determine opsonic activity in these preparations forStaphylococcus epidermidis; Haemophilus influenzae type b; Streptococcus pneumoniaeserotypes 3, 14 and 19; Group BStreptococcussero-types Ia, Ib, Ia/c, II and III; andEscherichia coli(K1). Pathogen-specific osponic activity of the lots tested ranged from undetectable to 1:80 and was detectable in < 10% to >90% of lots tested depending on the organism and manufacturer. Within an IVIG lot there was variable opsonic activity against different strains or serotypes of the same organisms. Opsonic activity was significanlty (P≤ 0.05) affected by the manufacture's donor pool and less so by the manufacturing method. We conclude that the pathogen-specific opsonic antibody activity of an IVIG lot is: (1) highly variable for several common neonatal pathogens; (2) predominantly dependent on the donor pool and not the manufacturing method. Clinicians may more appropriately select therapy if the pathogen-specific antibody content of IVIG products by lot are known. In the future neonatal IVIG research should focus on using preparations with known pathogen-specific anti-body activity.