Renal damage frequently complicates perinatal asphyxia. Renal vasoconstriction due to adenosine metabolite leads to a fall in glomerular filtration rate (GFR) and filtration fraction. This might be inhibited by the nonspecific adenosine receptor antagonist, theophylline. This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. We randomized 40 severely asphyxiated term infants to receive intravenously a single dose of either theophylline (5 mg/kg; study group: n=20) or placebo (control group: n=20) during the first hour of life. Fluid intake, urine output, serum creatinine, creatinine clearance, GFR, urinary beta2 microglobulin (beta2 M) and sodium excretion were recorded during the first 5 days of life. The two groups were comparable. No significant difference was reported regarding mechanical ventilatory support, respiratory complications and seizures. Severe renal dysfunction was significantly higher in the control group. Serum creatinine values were less, and creatinine clearance and GFR were significantly higher in the theophylline group from the second day onwards. beta2 M excretion was significantly less in the theophylline group, while sodium excretion and hematuria showed no significant difference. Prophylactic theophylline treatment, given early after birth, has beneficial effects in reducing the renal involvement in asphyxiated full-term infants, with no significant changes in central nervous system involvement.