Phosphorus-31 magnetic resonance spectroscopy (MRS), able to detect membrane metabolism and intracellular pH as well as energy metabolism in vivo, was applied to 17 bipolar patients in the manic state and the euthymic state. In nine of these patients, brain lithium concentration was simultaneously determined by means of lithium-7 MRS in order to clarify the effect of treatment with lithium on brain phosphorous metabolism. Both phosphomonoester (PME) peak area and intracellular pH were found to be higher in the manic state than in the euthymic state. These values in the euthymic state were lower than those in normal controls whose ages and sexes were matched with the patients. However, PME and intracellular pH did not correlate to brain lithium concentration. These findings coincide with a hypothesis that patients with bipolar disorder may have membrane abnormality in their euthymic state and state-dependent alteration of catecholaminergic activity may be a secondary phenomenon.