The effects of the tricyclic antidepressant imipramine and the atypical antidepressant mirtazapine were compared on the performance of rats in three operant procedures: a differential reinforcement of low rates schedule (DRL), a delayed matching to position (DMTP), and simultaneous visual discrimination tasks. Both compounds improved performance in the DRL task in a similar dose-related manner. Imipramine, but not mirtazapine, disrupted performance in the visual discrimination task. Imipramine reduced accuracy and increased response latencies and missed trials. Neither compound effected accuracy in the DMTP; both compounds caused some slowness of responding and imipramine caused several animals to fail to respond in a manner similar to that observed in the visual discrimination task. These data suggest that although imipramine and mirtazapine are similarly effective in putative tests of antidepressant activity, imipramine has a greater tendency to disrupt other aspects of cognitive performance, as well as exert generally depressive effects on operant responding. (C) 1994 Wiley-Liss, Inc.