Previous studies using a mixed beta1 and beta2 adrenergic antagonist, propanolol, have indicated that beta adrenoceptors have little effect on the cognitive functioning of the prefrontal cortex. However, recent studies have suggested that endogenous stimulation of beta1 adrenoceptors impairs working memory in both rats and monkeys. Since propanolol has no effect on cognition, we hypothesized that activation of beta2 adrenoceptors might improve performance in a working memory task. We tested this hypothesis by observing the effects of the beta2 agonist, clenbuterol, on spatial working memory performance. Clenbuterol was either infused directly into the prefrontal cortex (rats) or administered systemically (monkeys). Results demonstrated that clenbuterol improved performance in many young and aged rats and monkeys who performed poorly under control conditions. Actions at beta2 adrenoceptors were confirmed by challenging the clenbuterol response with the beta2 adrenergic antagonist, ICI 118,551. The effects of clenbuterol were not universal and depended on the cognitive status of the animal: the drug moderately improved only a subset of animals with working memory impairment.