Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.