An hypothesis based on the original stress model of depression, learned helplessness, proposed that exposure to uncontrollable stress provides the basis, in animals as in humans, for learning that stress is uncontrollable (helplessness); this learning has a number of debilitating consequences, including depression. This study suggests that rats subjected to daily restraint sessions (1h × 5 d, in 20 × 10 × 10 cm boxes) displayed a quiescent behavior vvith few attempts to escape from the box during the restraint periods, and subsequently exhibited escape deficits in a shuttle-box. These deficits were eliminated by clomipramine (8 or 16 mg/kg), imipramine (16 mg/kg) and nialamide (16 mg/kg) given twice daily subsequent to the last restraint session. In contrast, diazepam (2 mg/kg/d) or sulpiride (8 mg/kg/d) did not reduce helpless behavior induced by daily restraint sessions. In addition reduction in locomotor activity has been reported in rats subjected to restraint. It is suggested that the experience of loss of control thought to result from unsuccessful attempts to escape the stressor could be the critical aspect of behavior sensitive to antidepressants.