We hypothesized that because bilirubin is a potent free-radical quencher, infants without disorders that have oxygen-radical disease (ORD)-mediated mechanisms may have higher bilirubin levels than infants suffering from conditions possibly associated with ORD-mediated mechanisms (e.g., necrotizing enterocolitis, broncopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity). We identified 25 infants (birth weight 912 +/- 208 gm, gestational age 27 +/- 3 weeks) who comprised the ORD group and compared them with 57 controls (birth weight 1242 +/- 248 gm, gestational age 31 +/- 3 weeks). Infants with ORD had lower peak serum bilirubin concentrations, later ages at peak, and lower incidence of peak bilirubin concentrations exceeding 10 or 15 mg/dl. In addition, these infants exhibited a slower rate of bilirubin rise and a smaller area under the bilirubin-time curve measure compared with controls. To control for different birth weights, we analyzed subgroups weighing < 1000 gm. Significant differences were again identified in peak bilirubin concentrations, age at peak, phototherapy duration, and area under the curve. In this population of preterm infants, higher bilirubin levels were associated with a lower incidence of oxygen radical-mediated injury.