Five-day-old infant rats which acquire Haemophilus influenzae b bacteremia and meningitis after intranasal inoculation have a transient depression in weight gain (2 days), but then continue to grow at the same rate as strain U--11 inoculated controls. Brain lactate, glucose, and glycogen concentrations increase during the first 5 days of disease in infected animals. The increase in brain glycogen can be accounted for by an influx of glycogen containing polymorphonuclear leukocytes. The increased concentrations of glucose and lactate were found not to be due to a change in brain weight to dry weight ratio or the volume of entrapped blood. The mean cerebrospinal fluid (CSF) glucose concentration was higher in animals with meningitis (2.7 mM) in comparison to U-11 inoculated controls (1.8 mM). This increase in brain and CSF glucose concentration appeared secondary to an increased brain uptake of hexoses as manifested by an increased [3H]mannitol uptake. Brain lactate accumulation was not explicable from the data available. There was no evidence of cerebral cortical cellular damage because in vitro oxygen uptake and lactate production were equivalent in control and meningitic animals. The ability of the infant rat brain to maintain cerebral adenosine triphosphate (ATP) content in menigitis and the failure of CSF glucose concentration to decrease might be a reflection of the importance of alternative oxidative substrate (e.g., beta-hydroxybutyrate) to the cerebral metabolism of the developing rat brain.