Prelimbic-infralimbic cortex (PL-IL) and orbitofrontal cortex (OFC) influence behavioral flexibility in the rat. The authors tested the effects of PL-IL or OFC infusion with the GABA agonist muscimol in the context of 2 flexible responding tasks: strategy switching and reversal. Muscimol infusion into PL-IL impaired retention of strategy switches but not reversals, whereas muscimol infusion into OFC impaired retention of reversals but not switches. However, whereas training in repeated reversals did not remove the requirement of PL-IL for switch retention (E. L. Rich & M. L. Shapiro, 2007), training in repeated switches did remove the requirement of OFC for reversal retention. Thus, activity during strategy switches was sufficient to initiate learning and remove the requirement of OFC in later reversals.