Fibronectin is a large-molecular-weight glycoprotein present on most cell surfaces, in extracellular fluids, and in plasma. Both cell-associated and soluble fibronectin are thought to have important roles in the inflammatory response and host defense and may contribute to the maintenance of microvascular integrity during septic episodes. Newborn infants have levels of fibronectin in plasma that are one-third to one-half those found in the healthy adult. In addition, neonates with respiratory distress syndrome, perinatal asphyxia, bacterial sepsis, intrauterine growth retardation, or postnatal malnutrition have a further depression in their plasma levels of fibronectin. The low plasma concentration of fibronectin in newborn infants may contribute to the hypofunction of the neonatal reticuloendothelial system and predispose to the development of sepsis. Rates of synthesis of plasma fibronectin are diminished in the neonate, and an inverse correlation between fibronectin half-life and gestational age exists. The role of fibronectin in treatment or prophylaxis of neonatal sepsis remains to be determined.