The effects of hyperoxia on the entry of bilirubin and albumin into the brain were studied in five to six-week-old male Sprague-Dawley rats. Bilirubin was infused at 20 mg/kg/hour for three hours through a carotid catheter, resulting in serum bilirubin levels of 200-220 microM at 180 minutes. Group 1 (n = 8) was normoxic at all times. Group 2 (n = 8) was given oxygen (FiO2 = 0.75 -0.80) for the last hour of the three-hour bilirubin infusion. Group 3 (n = 10) was given oxygen (FiO2 = 0.75 -0.80) for 24-27 hours prior to, as well as during the bilirubin infusion. No significant differences were found in brain bilirubin (as measured by chloroform extraction) or brain albumin (as measured by 125I-albumin uptake) between the groups. Under these experimental conditions, hyperoxia does not increase bilirubin deposition in rat brain nor does it cause opening of the blood-brain barrier as measured by albumin entry into the brain.