Neuropsychological studies of subjects with bipolar disorder suggest impairment of working memory not only in acute mood states, but also while subjects are euthymic. Using fMRI to probe working memory regions in bipolar subjects in different mood states, we sought to determine the functional neural basis for these impairments. Typical working memory areas in normal populations include dorsolateral prefrontal cortex (BA9/46) and the posterior parietal cortex (BA40). We evaluated the activation in these regions using an n-back task in 42 bipolar subjects (13 manic, 15 euthymic and 14 depressed subjects) and 14 control subjects. While both control and bipolar subjects performed similarly on the task, bipolar subjects in all three mood states showed a significant reduction in activation in right BA9/46 and right BA40. Patients with bipolar disorder exhibit significantly attenuated neural activation in working memory circuits, independent of mood state. The reduction of neural activation may suggest a trait-related deficit. Subjects with bipolar disorder activated other additional frontal and temporal regions, perhaps as a compensatory mechanism, but this remains to be further explored.