Injection of beta-lactam antibiotics (reterpen, ceftazidime, and thienam) to mice in doses equivalent to the mean therapeutic doses for humans led to shortening of the duration of behavioral despair in the hanging by the tail test, modified the resistance to serotonin edema, and intensified the exploratory and orientation activity in the open field test. This sum of effects was detected after 10 injections of retarpen and thienam and after single and five-fold administration of ceftazidime. Antidepressant sertraline also shortened the duration of behavioral despair and reduced serotonin edema. An inverse correlation between the duration of behavioral despair and severity of serotonin edema was detected in control mice. The results suggest that beta-lactam antibiotics are characterized by antidepressant effect related to changes in serotonin sensitivity.