The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37°C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo-[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p<0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50–65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (P<0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxiaischemia, as occurs in adults. A late hypoperfusion takes place that results from rather than causes tissue necrosis seen histologically at 15–50 h of recovery. The results suggest that therapeutic attempts to improve CBF by reducing cerebral edema after hypoxia-ischemia will not alter ultimate neuropathologic outcome.