PURPOSE: To demonstrate the feasibility of three-dimensional echo-planar spectroscopic imaging (EPSI) at short echo time (13 msec) with a conventional clinical imager in the human brain. MATERIALS AND METHODS: Periodic inversions of a readout gradient were used during data acquisition to simultaneously encode chemical shift and one spatial dimension in one excitation. Aliasing artifacts were avoided with a modified acquisition-and-processing method based on oversampling. A double outer-volume suppression technique that adapts to the ovoid brain shape was used to strongly reduce extracranial lipid resonances. RESULTS: Three-dimensional spatial encoding in vivo of eight sections with 32 x 32 voxels each (0.75 cm3) was performed in 34 minutes with four signal averages. The spectral resolution and signal-to-noise ratio (S/N) of resonances of inositol, choline, creatine, glutamate and glutamine, and N-acetyl aspartate were consistent with those previously recorded with conventional phase encoding. CONCLUSION: EPSI substantially reduces acquisition time for three-dimensional spatial encoding and yields a spectral quality similar to that obtained with conventional techniques without affecting the S/N per unit time and unit volume.