Studies of depressed adults have shown abnormalities in cerebral energy metabolism, as noted by low brain levels of nucleoside triphosphate (NTP), which primarily represents adenosine triphosphate (ATP). This study was undertaken to determine whether proton magnetic resonance spectroscopy (¹H MRS) measures of the low-field purine resonance, which arises primarily from adenosine phosphates, can be used to assess abnormalities in cerebral purine metabolism in depressed adults. Data from ¹H MRS and phosphorus-31 (³¹P) MRS were acquired for depressed and nondepressed comparison subjects. Intensities of the purine resonance, by ¹H MRS (7.5–8.5 ppm), and of NTP, by ³¹P MRS, were determined. Purine resonance intensities did not differ on average between depressed patients and comparison subjects. However, purine levels were approximately 30% lower in female depressed subjects who subsequently responded to fluoxetine treatment than in those who did not respond. Beta-NTP was lower by 21% in responders than in nonresponders and was correlated with purine levels for the depressed subjects. Brain purine levels are low in female depressed patients who respond to treatment with fluoxetine, suggesting that response to treatment might be predicted by using ¹H MRS. These observations also suggest that agents that increase brain adenosine levels may have antidepressant efficacy.