Cerebral microembolism was performed in rats by injecting radioactive calibrated 50 mu microspheres into the left internal carotid artery. The use of radioactive microspheres as embolic agents enabled the number of microspheres to be determined in each cerebral hemisphere. Edema was assessed 24 h after embolization by measuring brain water, sodium, and potassium content. Equiosmolal doses (40 mmol/kg) of glycerol or urea were injected i.p. at various times before sacrifice. Both treatments caused similar changes in water and electrolyte content, brain dehydration being maximal 30 min after urea and 2 h after glycerol injection. Cerebral energy metabolism and regional blood flow were evaluated at the times of maximal brain dehydration. Urea treatment resulted in an improvement of the cerebral circulation whereas glycerol treatment led to a deterioration of cerebral blood flow which cannot be explained by failure to reduce edema and the consequent microcirculatory impairment. Urea treatment had no marked effect on cerebral energy metabolism whereas glycerol injection resulted in an important increase in brain lactate level which may be relevant to the impairment of cerebral reperfusion. These results point out that administration of a metabolized solute like glycerol may exert deleterious effects on the ischemic brain.