We studied cerebral blood flow (CBF) autoregulation and intracranial pressure (ICP) during normo- and hyperventilation in a rat model of Streptococcus pneumoniaemeningitis. Meningitis was induced by intracisternal injection of S. pneumoniae Mean arterial blood pressure (MAP), ICP, cerebral perfusion pressure (CPP, defined as MAP-ICP) and laser-Doppler CBF were measured in anesthetized infected rats (N=30) and saline-inoculated controls (N=30). CPP was either incrementally reduced by controlled haemorrhage or increased by intravenous norepinephrine infusion. Twelve hours post-inoculation, rats were studied solely during normocapnia, whereas rats studied after 24 hours were exposed to either normocapnia or to acute hypocapnia. In infected rats compared to control rats, ICP was unchanged at 12 hours, but increased at 24 hours post-inoculation (NS and P<0.01, respectively); hypocapnia did not lower ICP, compared to normocapnia. Twelve hours post-inoculation, CBF autoregulation was lost in all infected rats, but preserved in all control rats (P<0.01). Twenty-four hours after inoculation, 10% of infected rats had preserved CBF autoregulation during normocapnia in comparison to 80% of control rats (P<0.01). In contrast, 60% of the infected rats and 100% of the control rats showed an intact CBF autoregulation during hypocapnia (P<0.05 for the comparison of infected rats at normocapnia vs. hypocapnia). In conclusion, CBF autoregulation is lost both at 12 and at 24 hours after intracisternal inoculation of Streptococcus pneumoniae in rats. Impairment of CBF autoregulation precedes the increase in ICP, and acute hypocapnia may restore autoregulation without changing the ICP.