The effects of exogenous Cushing's syndrome on the brain metabolism were investigated by proton magnetic resonance spectroscopy (MRS). Thirteen patients having been treated for 2 to 22 years with prednisone were recruited. On the average, none of the metabolites (NAA, Cr, Cho and mI) were significantly different from those of 40 normal subjects in any of the three regions studied: frontal area, thalamus and temporal area. However, the Cho/H(2)O ratios were found to decrease significantly in the thalamic area as a function of treatment period (-1.3%/year). In the frontal and temporal areas, decreases of the Cho/H(2)O ratios were measured with treatment period but they did not reach statistical significance. Effects on Cho levels can be related to those observed for patients with endogenous Cushing's syndrome and suggest an impairment at the membrane level. The Cho/H(2)O reductions were not found to be dose- or age-dependent. Other metabolite ratios did not vary with treatment period, dose or age.