The metabolic basis of the encephalopathy associated with acute bacterial meningitis is unknown. The presence of cerebrospinal fluid lactic acidosis and hypoglycorrhachia suggests that intracellular acidosis or cellular energy depletion may play a role. Phosphorus magnetic resonance spectroscopy allows for the noninvasive determination of intracellular pH and relative amounts of phosphate-containing metabolites in humans. In seven normal volunteers, the intracellular pH of a mixed volume of gray and white matter was 7.00 +/- 0.04 (mean +/- SD). The apparent relative intensities of resonances from adenosine triphosphate, phosphocreatine, phosphodiesters and phosphomonoesters, and inorganic phosphate were measured. An encephalopathic patient with pneumococcal meningitis who had severe cerebrospinal fluid lactic acidosis was studied. Brain intracellular pH and relative phosphate metabolite concentrations were normal. Intracellular acidosis and bioenergetic compromise are therefore not causes of encephalopathy in this disease. This also demonstrates that the human brain can maintain tight control of intracellular pH even in the presence of marked extracellular metabolic acidosis.