Sepsis and meningitis continue to be a major cause of morbidity and mortality in human neonates, especially those who are born prematurely. This is likely due to several defects in host resistance in the term and premature infant. Early studies from our laboratory (J. Clin. Invest. 48:1379, 1976), indicated that opsonic antibody deficiency was a major risk factor for neonates who develop group B streptococcal (GBS) disease. Moreover, human infants and experimental animals infected with GBS often develop a profound neutropenia and depletion of bone marrow neutrophil storage pools during infection (Pediat. Res. 14:806, 1980). Administration of specific antibody in whole blood transfusions (Lancet 1:636, 1978), IVIG (J. Pediat. 99:873, 1981; J. Pediat. 118:606, 1991) or murine (J. Infect Dis. 149:363, 1984; J. Infect. Dis. 153:1170, 1986) or human monoclonal antibody preparations (J. Infect. Dis. 163:792, 1991) is often able to significantly decrease mortality from GBS disease, while at the same time correcting or preventing the severe neutropenia and depletion of marrow granulocyte reserves. This is likely due to the release of complement derived chemotactic and leukocyte releasing factors (Amer. J. Pathol. 133:623, 1988; J. Infect. Dis. 150:64, 1984; J. Immunol. 148:1879, 1992). Thus, a small breakdown product of C3b, C3dg, appears to promote the prompt release of marrow granulocytes while C5a, the major chemoattractant derived from complement, enhances the release of local inflammatory cytokines such as tumor necrosis factor (TNF), IL-8 and interferon (Amer. J. Pathol. 133:623, 1988; J. Invest. Med. 45:146A, 1997). These, along with C5a itself, promote the local accumulation and activation of neutrophils at the site bacterial invasion. Interferon also enhances the chemotactic response of PMNs from neonates and corrects the defect in signal transduction observed in these cells (J. Exp. Med. 173:767, 1991). Thus, host defenses in the neonate depend upon a well ordered interplay between specific antibody, complement components, white blood cells and inflammatory cytokines. Immunotherapy of neonatal infection in the future may well involve the use of specific polyclonal or monoclonal antibodies along with recombinant human cytokines or complement derived inflammatory mediators.