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The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant‐like activity. The behavioral despair and the tail suspension tests are based on the same principle, measurement of the duration of immobility occurring following exposure of rodents to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility. Curr. Protoc. Pharmacol. 38:5.8.1‐5.8.11. © 2007 by John Wiley & Sons, Inc.