Magnetic resonance spectroscopy (MRS) is a non-invasive tool for in vivo chemical analysis. We have been studying brain metabolism in patients with affective disorders using ³¹P-MRS and ¹H-MRS. The results of these studies are summarized as follows: (1) Phosphomonoester (PME) peak was elevated in manic patients with bipolar disorder (12.3±1.9%, n=17). PME was lower in the euthymic state (10.2±1.5%, n=17) than that in normal controls (11.4±1.6%, n=17). (2) Phosphocreatine (PCr) was lower in the left frontal lobe in bipolar depression (8.4±1.0%, n=11) compared with normal controls (9.8±1.1%, n=21). Decrease of PCr correlated with higher scores in Hamilton Depression Rating Scale (r= −0.75). PCr in the frontal lobes was low in all psychiatric states in patients with bipolar II disorder. (3) Intracellular pH was lower in euthymic patients with bipolar disorder treated with lithium (7.01±0.04, n=40) than normal controls (7.05±0.04, n=60), while it did not differ from controls in manic or depressive states. (4) The choline containing compounds (Cho) measured by ¹H-MRS was increased in both bipolar and unipolar depression in the basal ganglia. Decrease of PCr is of particular interest because PCr was increased in the left frontal lobe in schizophrenia. This may provide a clue to clarify the biochemical difference in bipolar disorder and schizophrenia. Alteration of intracellular pH is also of interest because it may relate to clinical action of lithium. These findings will provide new research strategies to study the neurochemical basis of bipolar disorder.