A depression-like state was induced in Wistar rats by chronic (3-week) exposure to very mild, unpredictable stress, which led to diminished food consumption and diminished preference for sweet drinks (anhedonia). Anhedonia was then abolished by 5 weeks of daily administration of imipramine to the continually stressed animals. One day after the last drug injection and stressful event, a statistically significant decrease in the proliferative activity of splenocytes to Con A stimulation in vitro was observed in those animals. Eight weeks of stress (without antidepressant therapy) affected likewise, but in a less potent and non-significant manner, the activity of splenocytes. Administration of imipramine alone for a period of 5 weeks did not modify the activity of these cells.