A depression-like state was induced by chronic (3-week) exposure of Wistar rats to a very mild, unpredictable stress which is a model of depression, developed by Willner's group. Five-week daily administration of imipramine reversed the stress-induced deficit in sucrose consumption. Eight-week stress induced an increase in the ability of splenocytes to produce interleukin 1 (IL-1) and interleukin 2 (IL-2) and to proliferate after stimulation with concanavalin A. Antidepressant effects of imipramine were accompanied by a decrease in the ability of splenocytes to produce IL-1 and IL-2 and to proliferate. Administration of imipramine alone did not modify the activity of those cells.