Clinical studies on spontaneous confabulation and imaging studies with healthy subjects indicate that the anterior limbic system, in particular, the orbitofrontal cortex (OFC), is necessary to adjust thought and behavior to current reality. It appears to achieve this by continuously suppressing activated memories that do not pertain to ongoing reality, even before their content is consciously recognized. In the present study, we explored through what anatomical connections the OFC exerts this influence. Healthy subjects were scanned with H 2 15 O PET as they performed four blocks of continuous recognition tasks, each block composed of a different type of stimuli (meaningful designs, geometric designs, words, nonwords). Within each block, three runs composed of exactly the same picture series, arranged in different order each time, were made. Subjects were asked to indicate item recurrences only within the currently ongoing run and to disregard familiarity from previous runs. In the combined first runs, in which all items were initially new and responses could be based on familiarity judgement (with repeated items) alone, we found medial temporal and right orbitofrontal activation. In the combined third runs, when all items were already known and selection of currently relevant memories was required, we found left orbitofrontal activation contingent with distinct activation of the ventral striatum, head and body of the caudate nucleus, substantia nigra, and medial thalamus. The study indicates that the OFC influences the cortical representation of memories through subcortical connections including the basal ganglia and the thalamus. The data are compatible with a role of the dopaminergic reward system in the monitoring of ongoing reality in thinking.