In an earlier study in dogs we found a reduced cerebral blood flow measured intermittently during the first hours after an intravenous injection of E. coli endotoxin. Within 5 min after the endotoxin injection, a temporarily reduced cerebrospinal fluid pressure was seen irrespective of changes in arterial blood pressure. One possible explanation for this could be an early reduction of the blood flow in the brain. To test this hypothesis, the initial flow reaction was evaluated by measurement of the blood flow in the superior sagittal sinus using an electromagnetic probe around the intact sinus. In five animals following E. coli endotoxin 1.0-1.5 mg/kg intravenously, the superior sagittal sinus blood flow decreased within 2 min, followed by increasing flows within 15 min and thereafter continuously decreasing values up to 60 min, thus giving a two-phase vascular reaction. In all animals there was a marked initial increase in cerebrovascular resistance and the fall in blood flow was thus not a mere consequence of blood pressure changes. In three other animals pretreated with methysergide, a serotonin antagonist, no increase in cerebrovascular resistance was seen during the initial phase. Later, the reaction was similar in all eight animals.