A localized two-dimensional (2D) 1 H MR chemical exchange spectroscopic (L-EXSY) sequence has been implemented on a whole-body 1.5-T MRI/MRS scanner. The second spectroscopic encoding to monitor the chemical exchange was an integral part of the single-volume localization using three sliceselective 90°radiofrequency (RF) pulses, thereby eliminating the need for any additional RF pulses, off-resonance/continuous wave saturation, or selective inversion, which are essential in the one-dimensional 1 H MR exchange spectroscopy. Even though the TM-crusher dephased single-and higher-order multiple-quantum coherences, the zero-quantum coherences were indistinguishable from the longitudinal magnetization leading to J-coupled 2D cross peaks similar to COSY. With TM of 300 ms, two different exchange cross peaks were recorded in human calf muscle: a first peak, between the mobile tissue water and total creatine pools, and a second peak, possibly between the olefinic and magnetically equivalent poly methylene protons of A strong reduction in the signal from free water is observed in the conventional magnetization transfer (MT)-based MRI techniques when an off-resonance saturation pulse is transmitted with its carrier frequency positioned within the broad envelope of the immobile proton pool (1,2). Two possible mechanisms contributing to this transfer are: (i) chemical exchange of protons from an immobilized macromolecule associated state to free water and (ii) dipolar relaxation between the saturated, immobile protons and the unbound water protons (3).Dreher et al. first reported a large intensity reduction in the creatine/phosphocreatine (Cr/PCr) methyl singlet at 3.0 ppm while recording the 1 H MR spectra (MRS) of rat brain by using a 3-s long off-resonance saturation pulse prior to the conventional CHESS suppression of water on a 4.7-T MRI scanner (4). Less significant changes were also reported in other cerebral metabolite resonances such as N-acetylaspartate (NAA) and choline (Ch) at 2.0 and 3.2 ppm, respectively (5). Using an off-resonance radiation (2.1 kHz from the water resonance) in healthy human brain, reductions in the N-methyl and N-methylene resonances of Cr/PCr were reported using a 2-T MRI scanner (6). However, no attenuation of the resonances of NAA, Ch, and other metabolites such as myo-inositol, glutamate, and glutamine was reported (6). Meyerhoff reported significant attenuations of creatine-containing metabolites in three different healthy human brain regions using a 1.5-T MRI scanner (7). A similar reduction in the creatine methyl resonance was recorded in the rat skeletal muscle using a 4.7-T MRI scanner (8).With the MRS voxel volumes range 36 -175 cm 3 , selective inversion of water resonance showed a significant reduction of the N-methyl protons of Cr/PCr in both human brain (10%) and skeletal muscle (25%) at 1.5 T (9). No significant reductions in Ch and NAA in human brain and Ch and lipids in human muscle were reported (9). The precise mechanism responsible for the magnetization transfer effect on t...