Cerebrovascular and cardiac alterations evoked by intravascular volume expansion with whole blood, a popular adjunct in the clinical prevention or therapy of the focal ischemic deficits of cerebral vasospasm and acute stroke, were studied in splenectomized dogs. Clipping of the right distal internal carotid and proximal middle cerebral arteries in eight dogs reduced regional cortical blood flow (rCoBF) by 49% to 58% without altering cardiac output (CO), and produced about 10% hemispheric infarction. Eight dogs underwent similar cerebral arterial occlusion and eight dogs underwent arterial manipulation without clipping. Both latter groups received two autologous whole blood infusions within 2 hours, each equal to 20% of the respective dog's total blood volume. Despite significant CO elevations after the infusions, rCoBF in the middle cerebral arterial territory did not rise. These whole-blood infusions did not significantly alter mean arterial blood pressure, hematocrit, intracranial pressure, or, in dogs with clipped cerebral arteries, the relative size of infarction. These data suggest that nondilutional hypervolemia neither elevates collateral perfusion to ischemic regions of the brain nor reduces infarction. In addition, elevations in CO do not appear to augment blood flow in either ischemic or normal brain.