Twelve pigeons key-pecked under a multiple variable interval 15-s, 150-s schedule of food reinforcement. The effects of methadone were studied alone and in combination with chronic daily administration of either imipramine (IMI) or desipramine (DMI). Chronic IMI was also given following reductions in response rates by unsignaled delay-to-reinforcement (UDR). Acute administration of methadone produced dose-dependent reductions in response rates under both schedules of reinforcement. Chronic daily administration of IMI or DMI alone did not result in lasting changes in baseline responding. When administered in combination, chronic daily IMI significantly attenuated the rate-reducing effects of methadone, whereas neither a low nor a high dose of chronic daily DMI was effective. The same dose of chronic daily IMI failed to ameliorate response rate reductions under delayed reinforcement. The behavioral and neurochemical specificity of the antidepressant effect is discussed.