<jats:title>Abstract</jats:title><jats:p>We investigated the differences in the resting state corticolimbic blood flow between 20 unmedicated depressed patients and 21 healthy comparisons. Resting state cerebral blood flow (CBF) was measured with H<jats:sub>2</jats:sub><jats:sup>15</jats:sup>O PET. Anatomical MRI scans were performed on an Elscint 1.9 T Prestige system for PET‐MRI coregistration. Significant changes in cerebral blood flow indicating neural activity were detected using an ROI‐free image subtraction strategy. In addition, the resting blood flow in patients was correlated with the severity of depression as measured by HAM‐D scores. Depressed patients showed decreases in blood flow in right anterior cingulate (Brodmann areas 24 and 32) and increased blood flow in left and right posterior cingulate (Brodmann areas 23, 29, 30), left parahippocampal gyrus (Brodmann area 36), and right caudate compared with healthy volunteers. The severity of depression was inversely correlated with the left middle and inferior frontal gyri (Brodmann areas 9 and 47) and right medial frontal gyrus (Brodmann area 10) and right anterior cingulate (Brodmann areas 24, 32) blood flow, and directly correlated with the right thalamus blood flow. These findings support previous reports of abnormalities in the resting state blood flow in the limbic‐frontal structures in depressed patients compared to healthy volunteers. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.</jats:p>