Cerebrovascular and cardiac alterations evoked by intravascular volume expansion with low molecular weight dextran (LMD, molecular weight 40,000), an advocated adjunct in the clinical prevention or therapy of acute stroke and cerebral vasospasm, were studied in splenectomized dogs. Clipping of the right distal internal carotid artery and the proximal middle cerebral artery (MCA) in eight dogs decreased regional cortical blood flow (rCoBF) by 58% without changing cardiac output (CO), and caused 10% +/- 5% (SE) hemispheric infarction. Ten other dogs underwent similar cerebral arterial occlusion and were infused twice with LMD within 2 hours; each infusion equaled 20% of the respective dog's total blood volume. Both CO and rCoBF in the territory of the occluded MCA increased significantly by 119% +/- 13% and 42% +/- 6%, respectively. following the two LMD infusions. Although the mean arterial blood pressure was unaltered, the hematocrit decreased significantly and the intracranial pressure (ICP) increased significantly. The mean hemispheric infarction in these 10 treated dogs was 4% +/- 2%. Another nine dogs underwent arterial manipulation without clipping. Two hemodiluting LMD infusions, similar to those in the 10 dogs, significantly elevated CO and ICP but not rCoBF. These data suggest that hypervolemic hemodilution with LMD effectively elevates collateral perfusion to ischemic regions of brain distal to occluded MCA segments and concomitantly raises the CO and ICP.