Robust increases in locomotor activity are observed following administration of dizocilpine maleate (MK-801). The present study investigated the effects of prior apparatus experience and manipulation of the testing environment on locomotor activity following peripheral MK-801. Gerbils were given zero or nine sessions of apparatus exposure prior to testing with MK-801 (0.1 mg/kg ip) or saline. Sessions were 10 min in duration and separated by 24 h. As previously reported, naive animals treated with MK-801 were significantly more active relative to controls. Exposure to the apparatus for nine sessions resulted in a significant reduction in MK-801-induced activity, but did not alter the activity levels of control animals. To evaluate the effect of changes to the testing environment, animals previously evaluated in the familiar condition were retested in the identical apparatus relocated to a novel experimental room. MK-801-treated animals exhibited a significant increase in activity when tested in this novel environment while the locomotor activity of control gerbils was not significantly altered. The results illustrate the importance of repetitive testing and environmental changes as moderating variables in studies that evaluate locomotor activity. These data also indicate that the effects of MK-801 on activity are sensitive to prior experience with the apparatus and the novelty of the testing environment.