Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P < 1.7 x 10(-4)) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312 +/- 61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.