Patients with hyperthyroidism may show impaired performance on several neuropsychological tests that require complex visual discrimination, conceptualization, mental flexibility or organization. These neurocognitive impairments appear to be consistent with prefrontal lobe dysfunction. This pilot study was undertaken to characterize the metabolite profile in the right prefrontal cortex in six patients with untreated Graves' disease by using in vivo proton magnetic-resonance spectroscopy (1H-MRS). For comparison, 1H-MRS was also carried out in seven healthy controls. The choline/creatine (Cho/Cr) and N-acetyl aspartate/creatine (Naa/Cr) ratios were determined. Cho/Cr ratios of the hyperthyroid patients were significantly lower than that of controls (means +/- SD = 0.61 +/- 0.09 vs. 0.90 +/- 0.18, p = .05). The two groups did not differ in their Naa/Cr ratios. Follow-up data after antithyroid treatment were available in three patients: Cho/Cr ratios were higher after treatment (euthyroidism) than before treatment (1.06 vs. 0.55; 0.82 vs. 0.54; 1.15 vs. 0.76). Tentatively, these preliminary data are most consistent with reversible reductions in the concentrations of choline-containing compounds (especially glycerophosphocholine and phosphocholine) in the prefrontal area during hyperthyroidism. However, these findings await confirmation by a definitive study with a larger sample size. A possible explanation of the findings is an altered brain cholinergic-adrenergic balance in hyperthyroidism.