The objective of this study was to test the hypothesis that 4 weeks of lithium administration would be associated with changes in brain gray and white matter volumes in healthy individuals. Thirteen right-handed healthy volunteers (6 females, mean age = 25.9 +/- 10.0 years) were studied. 3D SPGR MRIs (TR=25 ms, TE=5 ms, slice-thickness= 1.5 mm) were acquired using a 1.5 T GE Signa Imaging System, at baseline and after 4 weeks of lithium administration at therapeutically relevant doses. Optimized voxel-based morphometry (VBM) analyses were conducted. Left and right dorsolateral prefrontal cortex and left anterior cingulate gray matter volumes increased significantly following lithium administration. Total white matter volume was increased, whereas total brain volume and total gray matter volume were not significantly changed following 4 weeks of lithium. Lithium treatment resulted in prefrontal regional gray matter volume increases in healthy volunteers, as well as increases in total white matter volume. Whether these changes are mediated by neurotrophic/neuroprotective or osmotic effects remains unknown. (c) 2007 Elsevier Ireland Ltd. All rights reserved.