The purine metabolite hypoxanthine accumulates with hypoxia ischemia and with reperfusion is converted to uric acid (UA). We hypothesized that elevated UA concentration is a marker of previous hypoxia ischemia and would identify infants at greatest risk for having subsequent intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL). We determined the relationship between UA concentrations in the first postnatal day and the development of severe IVH, PVL, or both in 58 infants of birth weight 865 +/- 177 gm and gestational age 27 +/- 2 weeks. Severe IVH developed in 10 (17%) infants and PVL in 3 (5.1%) infants. UA concentrations on day 1 (obtained at 16 +/- 4 hours) were 7.9 +/- 2.8 mg/dl and increased to 9.5 +/- 2.58 mg/dl on day 2. UA concentrations on day 1 were higher in infants with severe IVH/PVL versus those in infants with neither condition: 10.2 vs 7.3 mg/dl (p = 0.005). Infants with hyperkalemia on the second postnatal day had higher UA concentrations on the first day versus infants with normal potassium levels: 11.7 +/- 2 mg/dl versus 6.8 +/- 1.8 mg/dl (p < 0.0005). Infants with severe IVH/PVL had higher potassium levels on day 2 versus infants with neither condition: 11.9 vs 6.9 mg/dl (p < 0.048). By univariate analysis UA concentrations were significantly related to gestational age (p = 0.005) and birth weight (p = 0.03). Only UA concentration (p = 0.004) and gestational age (p = 0.02) were related to IVH/PVL. By multivariate analysis UA remained significantly related to IVH/PVL even when adjusted for other clinical variables, with an odds ratio estimate of 1.63 (95% confidence interval 1.16 to 2.31). In conclusion, higher UA concentrations on the first postnatal day were associated with the subsequent development of severe IVH/PVL and with subsequent hyperkalemia. Elevated UA concentrations in the first postnatal day may help to identify a subset of premature infants at greatest risk for having subsequent hemorrhagic ischemic injury.