The alterations of cerebral energetic metabolism and intracellular brain pH that occur during histotoxic hypoxia were estimated in mice by in vivo 31P nuclear magnetic resonance (NMR) spectrometry. The brain spectra obtained by means of chronically implanted surface coils connected to a special designed probe were recorded sequentially and continuously before, during, and after histotoxic hypoxia induced by an injection of potassium cyanide. The levels of PCr, ATP, inorganic phosphate, and intracellular pH estimated from the records of the 31P cerebral spectra and the cerebral cortical activity allow noninvasive monitoring of both the energetic metabolism and the functional state of the brain in unanesthetized animals. The time courses of these different parameters are largely the same as those obtained previously by invasive methods, however, the simultaneous and continuous monitoring performed in this study exhibits several unexpected dissociations between, respectively, onset of coma, decrease in PCr level and intracellular pHi, and recovery of normal levels of PCr and intracellular pH. These dissociations indicate that tissue acidosis plays a minor role in the changes in PCr levels, compared with ATP, and they confirm that the thresholds of oxidative metabolism required for functional tissue activity and a normal rate of ATP are clearly different.