Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.