The effects of arterial hypoxia on interstitial fluid adenosine concentrations were studied in the frontal cortex and thalamus by the brain dialysis technique and in CSF from the cisterna magna of the newborn piglet. Acute hypoxia (PaO2 = 20 +/- 1 mm Hg) increased the interstitial fluid adenosine concentrations significantly from 0.68 +/- 0.29 (SEM) to 1.60 +/- 0.35 microM in the frontal cortex and from 1.03 +/- 0.32 to 2.60 +/- 0.86 microM in the thalamus (n = 8). Interstitial fluid inosine and hypoxanthine also increased significantly during hypoxia. In separate groups of piglets, the adenosine concentration in the cisterna magna CSF under normoxic conditions was 0.04 +/- 0.01 microM (n = 5), which increased significantly to 0.17 +/- 0.04 microM (n = 6) with hypoxia (PaO2 = 4.7 +/- 1.2 mm Hg). Cisterna magna CSF inosine levels did not change significantly during the severe hypoxia. Adenosine concentrations found in the interstitial space and CSF of newborn piglets under normoxic and hypoxic conditions are within the vasodilator range. These results thus suggest that in the neonatal brain adenosine may play a role in regulating blood flow during hypoxia.