The intense intrathecal inflammation observed in acute bacterial meningitis (ABM) is associated with pronounced changes in cerebral blood flow (CBF) and metabolism. In seven substudies, CBF and metabolism were measured in adults with ABM as well as healthy volunteers during various interventions. Global and regional CBF was measured by transcranial Doppler ultrasonography, single-photon emission computed tomography, and the Kety-Schmidt method. Cerebral metabolism and net flux were measured by the Fick principle. Interventions included intravenous norepinephrine infusion, acute hyperventilation, propofol infusion, and mannitol infusion. Global CBF in patients was lower than that of controls; cerebral oxygen extraction and metabolism was lower in patients than in controls. Regional CBF was more heterogeneous in patients than in controls. Norepinephrine infusion increased mean arterial pressure and CBF, but not cerebral metabolism, and no cerebral net flux of catecholamines was found. Thus, autoregulation was impaired in the early phase of ABM; autoregulation was restored both by acute hypocapnia in the early phase of ABM and spontaneously during clinical recovery. CBF decreased during acute hypocapnia in patients as well as volunteers, although the variation in CO2 reactivity was larger among patients than among controls. Cerebral oxygen metabolism and the regional flow distribution in patients remained unchanged during hypocapnia. In patients, propofol infusion reduced cerebral metabolism more than it reduced CBF, indicating impaired cerebral metabolic coupling. Patients with ABM exhibited a marked efflux of tumour necrosis factor-alpha and interleukin-6 over the cerebrovascular bed. No such efflux was found in volunteers at baseline or following an intravenous bolus of endotoxin. The studies provide new information about pathophysiological changes, in particular regarding CBF, cerebral oxidative metabolism, and certain aspects of the inflammatory response during ABM. These findings may be important for supportive treatment of patients with this life-threatening disease.