OBJECTIVE To evaluate the relative importance of biochemical markers of antioxidant status, gestational age, and parameters of neonatal care in the clinical outcome of premature infants. METHODS A prospective, observational, longitudinal study of the association between these factors was conducted. Blood was collected from an in situ arterial line within two hours of birth and at intervals thereafter, when blood was drawn for routine clinical purposes. Outcome was assessed as death, or survival with or without bronchopulmonary dysplasia (BPD). One hundred and forty four babies of 22 to 39 weeks of gestation, who required intensive care at the Jessop Hospital for Women, between January 1993 and April 1994, were recruited. RESULTS Low gestational age at birth was the most important predictor of mortality and the development of BPD. Having corrected for gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Plasma vitamin C at birth was significantly higher in the babies who died compared with those with a good outcome, but this effect was not sustained after correcting for gestational age. Repeated measures of Analysis of Variance revealed a postnatal increase in antioxidant activity, caeruloplasmin, retinol, cholesterol corrected alpha tocopherol, and red blood cell superoxide dismutase (SOD) activity. Vitamin C, on the other hand, declined in all groups after birth. Logistic regression analysis revealed that the greater the number of packed cell transfusions received during intensive care, and the higher the concentration of vitamin C on the second day of life, the greater the risk of developing BPD. CONCLUSIONS After correcting for the effect of gestational age, low plasma antioxidant activity at birth was an independent risk factor for mortality. Frequent blood cell transfusions over the first week of life are associated with an increased risk of developing BPD. This association may be causal.