The human neonate is uniquely susceptible to serious and overwhelming bacterial and fungal infections. While deficiencies of antibody, complement, and T lymphocytes certainly contribute to this susceptibility, abnormal polymorphonuclear leukocyte function appears to be a major host defense abnormality in the neonate. Functional defects in neonatal polymorphonuclear leukocyte adherence, aggregation, movement, phagocytosis, and intracellular killing have been described in the term or preterm infant. Only recently, however, have the techniques become available to examine the biochemical and structural mechanisms underlying abnormal polymorphonuclear leukocyte function in the neonate. It now appears that there may be developmental defects in signal transduction, cell surface receptor upregulation and mobility, cytoskeletal rigidity, microfilament contraction, oxygen metabolism, and intracellular antioxidant mechanisms. Defining the biochemical and physiologic abnormalities in these cells may lead to therapeutic regimens for pharmacologically correcting these developmental defects in cell function.