Serious life-threatening neonatal infections with microbial species that are infrequently associated with infections in adults are related to the immature immune system of human newborn infants. The usually sterile intrauterine environment of the fetus is associated with a primed but inactive immune system at the time of birth. Sudden introduction into a complex microbial world stimulates the inflammatory system and an effective host defense rapidly develops. Defense mechanisms include innate phagocytic and complement systems, and specific adaptive immunity including antimicrobial antibodies. Fortunately, neonates have protective antibodies against many microbes at birth provided by their mothers via placental transfer of IgG. Specific antimicrobial antibody production by the newborn infant is delayed. Neutrophil numbers in the circulation are high in the normal neonate, but the bone marrow pool of cells is limited. Chemotactic responsiveness of circulating phagocytic cells is decreased in comparison with adult cells, although phagocytic and microbicidal activity of neonatal neutrophils and monocytes are normal. The newborn infant's lymphocyte system is relatively mature, and neonatal mononuclear cells have normal antigen-presenting and secretory function. T lymphocytes are present in normal numbers and although response of these cells to antigens is somewhat slower than in adult cells, a near normal response suggests intrauterine stimulation by maternally derived immunoregulators. B lymphocytes are also present in newborn human infants. However, maturation of B lymphocytes into antibody-producing plasma cells occurs gradually during the first weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)