Restraint stress, 6 h/day for 21 days, caused an impairment, during acquisition, of the performance of a spatial memory task, the eight-arm radial maze. The impairment was reversible, temporally limited and blocked by phenytoin, a blocker of excitatory amino acid action, or tianeptine, an antidepressant, which lowers extracellular serotonin. These effects on behavior parallel the reversible stress-induced atrophy of dendrites of hippocampal CA3 neurons that are also blocked by the drugs.