Over the past several decades, functional neuroimaging research has contributed to significant advances in understanding neural system abnormalities that underlie bipolar disorder (BD). Findings have converged to support dysfunction in a neural system that subserves emotional processing and regulation, which includes anterior paralimbic cortices and their subcortical connections sites, including amygdala and ventral striatum, as well as more rostral and lateral prefrontal cortices (1). Studies that focused on elevated, depressed, or euthymic mood states of the disorder suggest that some abnormalities are present only in individuals experiencing acute mood episodes of the disorder; whereas other abnormalities reflect the BD trait in that they are also present in euthymia. However, there are few studies that concurrently examined individuals in elevated, depressed, and euthymic mood states to clarify mood-state- and trait-related features. Such clarification may provide information important to understanding neural system features associated with vulnerability to, and recovery from, acute mood episodes and may suggest treatments to prevent or treat episodes of a particular valence, as well as markers of treatment response. Neural system findings associated with acute mood states of BD have primarily been in anterior paralimbic and more rostral and lateral cortices, including ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), rostral PFC (RPFC), and dorsolateral PFC (DLPFC). In comparison to healthy individuals, individuals with BD experiencing elevated mood episodes (including manic, mixed, or hypomanic episodes) have shown alterations in activation in these prefrontal regions at rest and in responses to activation tasks (2–7) that have tended to be decreases in the right hemisphere. These findings are consistent with lesions studies in which disinhibited manic-type states have been observed in association with frontal lesions, particularly when they occur in the right hemisphere (8–10). In individuals with BD experiencing depressive episodes, differences have tended to be in the left hemisphere and have tended to be activation increases (4, 11, 12), which may be elicited especially in response to negative emotional stimuli. For example, in one study in which faces of varying emotional expressions were presented, fearful face processing was associated with increases in left ventrolateral PFC activation (11). Recent functional neuroimaging investigations demonstrating dysfunction in VACC, OFC and RPFC during euthymia suggest dysfunction in these regions may be a trait feature of BD (4, 13–18), which is particularly elicited by emotional challenge and stimuli that may be of positive as well as negative valence (17, 19). Some studies have suggested that subcortical abnormalities may also be present across mood states of BD. Amygdala increases have been reported in manic, depressed, and euthymic mood states of BD, suggesting amygdala dysfunction may not be dependent on the valence of the mood state (11, 12, 20–33). However, there are some recent studies that suggest subcortical findings may be influenced by mood state, as there are reports of negative findings in euthymia and of abnormally increased amygdala activity that has been particularly associated with the depressed state in BD (17, 20, 34). The ventral striatum is highly implicated in BD because of its role in motivated behaviors, which are characteristically disrupted in acute mood episodes, such as in the disinhibited pursuit of motivationally-charged situations in mania and amotivated behavior in depression. The ventral striatum has less often been a focus in neuroimaging studies of BD although ventral striatal abnormalities have been reported in adults and adolescents with BD (11, 28, 35, 36). There are few neuroimaging studies that include individuals with BD in elevated, depressed, and euthymic mood states. A functional magnetic resonance imaging (fMRI) study in which individuals performed a color-word Stroop task showed decreased right OFC responses in association with elevated mood states, increased left OFC responses in association with depression, as well as an area of decreased left medial RPFC that was present across mood states (4). There were some consistencies between these findings and those of another fMRI study of the three mood states of BD during emotional processing. In that study, 12 manic, 12 depressed, and 18 euthymic individuals with BD, and 18 healthy individuals, were scanned while processing blocks of face stimuli depicting happy, fearful, or neutral expressions. Compared with healthy subjects, activation was reduced in OFC in individuals with BD across mood states and activation was also decreased in right DLPFC. No influence of the valence of the facial expression of the stimuli was detected (37). However, these findings were identified in an analysis that focused on specific regions of interest, and ventromedial PFC and RPFC regions were not assessed. The aim of the current study was to use an event-related fMRI design performed during implicit processing of positive, negative, and neutral faces by individuals with BD in elevated, depressed, and euthymic mood states to identify trait- and state-related abnormalities in neural system patterns of responses to the stimuli. We hypothesized ventral PFC decreases in responses would be present across mood states of BD, consistent with those decreases being trait features of the disorder. We further hypothesized that additional right PFC decreases would be associated with elevated mood states and that left PFC increases would be associated with depression. We anticipated amygdala and ventral striatal abnormalities (1, 24). We also explored wholebrain to assess whether there might be differences in other regions not hypothesized.