Behavioral depression through inescapable foot shock stress in Swiss albino mice was measured on the basis of their performance in an open field test (OFT) and a forced swimming test (FST). Glutathione (GSH) and various antidepressants (imipramine, maprotiline, fluvoxamine, trazodone, and alprazolam) were able to, either fully or partly, prevent and/or reverse the shock-induced behavioral depression. The GSH level was measured in the cerebral cortex, cerebellum, brain stem, and the hypothalamus in shocked mice to ascertain a possible correlation between brain GSH and stress-induced depression, under conditions of preshock and postshock antidepressant treatments as well as in the absence of the drugs. There was an appreciable depletion of cortical GSH in shocked mice that was corrected to varying degrees by the different antidepressants. The results suggest a close link between stress-induced behavioral depression, increased monoaminergic utilization, oxidative stress, and brain GSH.