Late-onset neonatal sepsis (LOS) remains an important cause of morbidity and mortality in premature babies. These infants are deficient in transplacentally acquired IgG and prevention of LOS with intravenous immunoglobulin (IVIG) has been studied by many groups with variable efficacy. Over the last decade, S. epidermidis has become a common cause of LOS. Analysis of multiple IVIG products has shown great variability in opsonic activity of IVIG for many pathogens including S. epidermidis. In the United States, three large double blind, placebo controlled trials evaluated the efficacy of IVIG for the prevention of LOS. One demonstrated efficacy and two did not. Analysis of the IVIG lots used in these studies demonstrated a correlation between opsonic activity for S. epidermidis and efficacy for LOS (Weisman, et al, Abstract, Society for Pediatric Research, 1996). In nurseries where S. epidermidis is an important pathogen, IVIG with opsonic activity for this organism may be critical to provide effective prophylaxis for LOS.