Evidence obtained to date indicates that beta adrenergic receptors in the brain may be involved in the effects of antidepressant drugs. Furthermore, it has been suggested that centrally acting beta adrenergic agonists might possess antidepressant activity. However, preclinical as well as clinical studies of the effects of beta adrenergic agonists have been limited due to the lack of compounds that penetrate into the central nervous system after peripheral administration. Recent results indicate that the beta adrenergic agonists clenbuterol and prenalterol are active centrally. For this reason, it was of interest to begin to assess their behavioral effects. It was found that clenbuterol and prenalterol, in a dose-dependent manner, reduced response rate and increased reinforcement rate under a differential-reinforcement-of-low-rate 72-sec schedule. The effects of these agonists were very similar to those of proven antidepressant drugs. The effects of the agonists clenbuterol and prenalterol, as well as the effects of the tricyclic antidepressant desipramine, on response and reinforcement rate were antagonized by the beta adrenergic antagonist propranolol. The present results indicate that clenbuterol and prenalterol are active behaviorally and that their effects appear to be mediated by beta adrenergic receptors. The similarity between the behavioral effects of the beta adrenergic agonists and those of proven antidepressant drugs provides evidence consistent with the contention that centrally acting beta adrenergic agonists might possess antidepressant activity.