Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.