Uric acid (UA) is a water-soluble antioxidant in human body fluids. In umbilical cord blood of 172 neonates with gestational ages between 22 and 42 weeks, UA concentrations were between 50 and 990 mumol/l. There was no correlation with gestational age. Infants with an umbilical cord pH < 7.0 had markedly lower UA concentrations in cord blood than neonates without severe acidosis. UA levels increased during the first 24 h of life and subsequently declined within 2 weeks to lower levels than in older children. In tracheal aspirates (TA), UA at concentrations of about 10(-4) mol/l was found capable of effectively scavenging free oxygen radicals. Luminol-dependent chemiluminescence activity of isolated TA phagocytes or alveolar macrophages was suppressed by UA dose dependently, with a 100% reduction at UA concentrations of 10(-3) mol/l. On the assumption that oxidative stress contributes to the development of chronic lung disease (CLD), in premature infants the ratio of the antioxidant UA and malondialdehyde (MDA) as a marker of oxidative injury was measured in serially obtained TA of 102 ventilated premature infants with birth weights < 1,500 g. At the age of 3-14 days, infants who later developed severe CLD had significantly lower TA UA/MDA ratios than infants without CLD development. In infants with moderate CLD, UA/MDA ratios were comparable to those in the non-CLD group until day 5. During the next 2 weeks, decreasing ratios of UA/MDA paralleled lung injury with increased oxygen requirement and microvascular permeability. Serum UA concentrations did not differ between groups. It is speculated that UA may be physiologically important as an antioxidant in the epithelial lining fluid of the respiratory tract in neonates during the 1st week of life.