Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these "therapeutic" effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal model of depression because the FSL rats do not appear to exhibit behaviors analogous to anxiety or schizophrenia and because they respond "therapeutically" to antidepressants and not psychomotor stimulants.