To evaluate a two-dimensional localized chemical shift correlated spectroscopy (L-COSY) sequence in elderly patients with major depression. A total of 33 healthy elderly subjects and 15 elderly patients with major depression were investigated. A voxel size of 3 x 3 x 3 cm3 was chosen in the dorsolateral prefrontal region with predominantly white matter, with the use of three slice-selective radiofrequency (RF) pulses (90 degrees , 180 degrees , and 90 degrees). A chemical shift-selective (CHESS) sequence was used prior to volume localization for the presaturation of water. The two-dimensional raw data matrix consisted of 1024 complex points along the detection period (t2), and 100 increments along the evolution period (t1), resulting in a total acquisition time of approximately 27 minutes per acquisition. The metabolite ratios were calculated using the two-dimensional peak volumes with respect to the diagonal peak volume of total creatine (Cr) at 3.0 ppm. In the 33 elderly subjects, the mean ratio of choline (Cho) to Cr was 10% higher in men compared to women (P < 0.05), consistent with earlier findings obtained by one-dimensional MRS. When the metabolite ratios were compared in a subsample of 16 elderly female controls and 12 depressed female patients, the depressed geriatric patients had higher levels of myoinositol (mI), phosphoethanolamine (PE), and glutamate/glutamine (Glx) than the controls, although the differences were not statistically significant. Our pilot study shows the feasibility of performing two-dimensional L-COSY successfully in elderly subjects and patients with late-life mood disorders. These findings are consistent with and expand on our earlier findings in major depressive disorder (MDD) detected with one-dimensional MRS.