Previously it was found that both acute and chronic antidepressant pre-treatment enhanced the locomotor hyperactivity induced by a challenge injection of the non-competitive NMDA receptor antagonist, dizocilpine (MK-801). In the present study the effects of acute and chronic antidepressant administration on phencyclidine (PCP)-induced locomotor hyperactivity were examined. Phencyclidine (PCP), a non-competitive NMDA receptor antagonist increased locomotor activity in rats. Fluoxetine given acutely increased and prolonged the PCP-induced locomotor hyperactivity, while citalopram, sertraline and paroxetine had no effect on the PCP-induced behavioural effect. Repeated treatment with fluoxetine, citalopram and paroxetine increased the PCP-induced locomotor hyperactivity. In contrast, chronic sertraline administration attenuated the locomotor response to a PCP challenge. These results indicate that these antidepressants which are presumed to have a similar pharmacological profile, differ in their ability to alter PCP-induced hyperactivity. Whether these differences have any bearing on the therapeutic or adverse effects of these drugs remains to be shown.