Acute administration of desipramine, mianserin and viloxazine produces a significant decrease of locomotor activity in rats. Conversely, the locomotion of rats receiving the antidepressants for a prolonged period of time is not modified with respect to control animals. Moreover, the reserpine-induced decrement of locomotion is not influenced by chronic treatment with any of the antidepressants used in the present study. Since tolerance develops rapidly to these behavioural effects they may be indicative of compensatory changes in neuronal systems which may occur during prolonged antidepressant treatment.