Behavioral flexibility is a concept often invoked when describing the function of the prefrontal cortex. However, the psychological substrate of behavioral flexibility is complex. Its key components are allocation of attention, goal-directedness, planning, working memory, and response selection. Furthermore, there is evidence that different regions of the prefrontal cortex might be implicated in these different components. In rule-switching tasks, a distinction is made between errors that are perseverative (difficulty switching from a previously rewarded strategy) and errors due to learned-irrelevance (difficulty switching to a strategy previously uncorrelated with reward). A similar distinction might be made for reversal learning, which involves inhibition of a previously rewarded response and activation of a previously unrewarded response. Damage to the orbital prefrontal cortex (OPFC) results in a deficit in reversal learning. The present study was designed to examine whether one or both of either perseveration or learned non-reward might account for the deficit. Rats with bilateral ibotenic acid-induced lesions of the OPFC were not impaired in acquisition of discriminations. They were impaired, relative to controls, only when they had to overcome learned non-reward. They did not show enhanced perseveration. We conclude that an inability to overcome learned non-reward significantly contributes to OPFC lesion-induced deficits in behavioral flexibility.