In a canine model of global cerebral ischemia, 6 dogs received a saline placebo prior to the event and 5 received 12.5 mg/kg ibuprofen. Cerebral venous outflow from the confluence of the sagittal and transverse sinuses, systolic and diastolic arterial pressure, cardiac output, pH, Paco2, Pao2, and arterial and sagittal sinus thromboxane B2 and 6-keto-PGF1 alpha were measured at intervals up to 120 minutes thereafter. Postischemic cerebral hypoperfusion was significantly improved in the ibuprofen pretreatment group. Control dogs showed significant increases in sagittal sinus postischemic thromboxane B2 concentrations, but pretreated dogs showed nearly complete inhibition of postischemic thromboxane B2 production. Pretreated dogs also had significantly lower levels of 6-keto-PGF1 alpha from the sagittal sinus. There were no significant differences in the other variables at any interval. We conclude that ibuprofen ameliorates postischemic cerebral hypoperfusion, and that this improvement is associated with decreased sagittal sinus levels of thromboxane B2 and 6-keto-PGF1 alpha.