We studied the effect of a synthetic copolymer surfactant, poloxamer 188, on cerebral blood flow in a rabbit model of focal cerebral ischemia. Following retro-orbital craniectomy, the parietal branch of the middle cerebral artery was occluded with bipolar current. Cerebral blood flow was measured by the hydrogen clearance technique using platinum-iridium electrodes placed within the parietal cortex. Ten rabbits were infused with 50 mg/kg poloxamer 188 in saline beginning 30 minutes after occlusion; 12 control rabbits received an equal volume of saline. Poloxamer 188 increased blood flow significantly in areas of severe or moderate ischemia but had little effect in areas with mild or no ischemia. The improvement in blood flow could not be accounted for by hemodilution, and the copolymer did not affect blood viscosity at any shear rate from 1 to 100 sec-1. We hypothesize that poloxamer 188 increases circulation in ischemic tissue by inhibiting adhesive interactions among proteins (fibrin and fibrinogen) and cells in the microcirculation.