Previous investigations examining the rat prefrontal cortex subregions in attentional-set shifting have commonly employed two-choice discriminations. To better understand how varying levels of difficulty influence the contribution of the prefrontal cortex to learning, the present studies examined the effects of orbitofrontal cortex inactivation in a two- or four-choice odor reversal learning test. Long-Evans rats were trained to dig in cups that contained distinct odors. In the two-choice odor discrimination, one odor cup was always associated with a cereal reinforcement in acquisition while the opposite odor cup was associated with a cereal reinforcement in reversal learning. In the four-choice odor discrimination, an additional two cups containing distinct odors were used that were never associated with reinforcement in acquisition or reversal learning. Bilateral infusions of the GABA-A agonist, muscimol (0.5 microg) into the orbitofrontal cortex did not impair acquisition of either the two- or four-choice discrimination task. However, muscimol infusions into the orbitofrontal cortex impaired two- and four-choice reversal learning. In the two-choice odor reversal, muscimol treatment selectively increased perseverative errors. In the four-choice odor reversal, muscimol treatment increased perseverative, regressive, as well as irrelevant errors. These findings suggest that the orbital prefrontal cortex not only enables task switching by supporting the initial inhibition of a previously relevant choice pattern, but under increasing task demands also enables the reliable execution of a new choice pattern and reduction of interference to irrelevant stimuli.