Metabolic consequences of hypothyroidism in adult human brain, despite neuropsychological symptoms, have not been reported. We used 31P nuclear magnetic-resonance spectroscopy of the frontal lobe to examine the effect of acute hypothyroidism on cerebral metabolism. Paired analysis showed that the phosphocreatine/inorganic-phosphate (PCr/Pi) ratio increased from a median of 2.04 (interquartile range 0.15) to 2.22 (0.25) after treatment with levothyroxine (p = 0.01). These reversible alterations in adult cerebral phosphate metabolism during acute hypothyroidism parallel PCr/Pi ratio changes described in skeletal muscle. This is the first direct evidence of cerebral metabolic effects of hypothyroidism on adult brain.