The bioenergetic status of the brain in scrapie mouse models was investigated during the late, clinical phase of the disease, by in vivo phosphorus magnetic resonance spectroscopy (MRS). The only significant change observed in the scrapie-infected mice compared with controls was an increase in intracellular brain pH (7.20+/-0.06 vs 7.10+/-0.05). No other changes in energetic metabolism were observed in the infected mice beside a trend in the decrease of phosphomonoester (PME) level, possibly associated with an alteration in glycolytic intermediates. This study showed that even in the presence of severe cellular vacuolation and microglia infiltrate, cerebral bioenergetic is maintained.