The effects of antidepressant drugs in rats responding under a differential-reinforcement-of-low-rate 72-sec schedule were assessed. Seven clinically used tricyclic antidepressant drugs (imipramine, desipramine, chlorimipramine, protriptyline, nortriptyline, amitriptyline and doxepin), two atypical antidepressants (iprindole and mianserin) and a monoamine oxidase inhibitor (tranylcypromine) dose-dependently reduced response rate and increased reinforcement rate. Nomifensine, an atypical antidepressant which has been reported to have psychomotor stimulant properties and abuse potential, increased response rate and decreased reinforcement rate. Chlorpromazine, an antipsychotic agent, and diphenhydramine, an antihistamine, have been reported to produce effects similar to antidepressants in several behavioral tests, but neither of these drugs mimicked the actions of antidepressants on responding under a differential-reinforcement-of-low-rate 72-sec schedule. Chlorpromazine decreased response rate but did not increase reinforcement rate. Diphenhydramine did not have consistent effects but tended to decrease reinforcement rate. These findings suggest that behavior maintained by the differential-reinforcement-of-low-rate schedule may be selectively affected by antidepressants that have no psychomotor stimulant properties.