The present study examined the effects of ethanol (0.75 g/kg IP) alone and in combination with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 (0.1 mg/kg SC) on the locomotor activity of rats. Sixteen rats were treated with vehicle plus saline, MK 801 plus saline, vehicle plus ethanol, and MK 801 plus ethanol. Locomotor activity was quantified for a period of 12 hours following drug administration. Ethanol was found to significantly decrease locomotor activity whereas MK 801 significantly increased locomotion during the first 2 hours postdrug. In addition, there was a significant additive interaction between ethanol and MK 801 during this time period. Two to four hours postdrug, MK 801 was observed to significantly decrease locomotion. Four to six hours postdrug, ethanol-treated rats had significantly increased locomotor activity whereas MK 801-treated rats displayed significantly decreased locomotion. No significant interaction was found between ethanol and MK 801 4 to 6 hours postdrug. No significant effects of any of the drugs on locomotor activity were observed from 6 to 12 hours postdrug. These results suggest that ethanol and MK 801 produce a pattern of effects on locomotor activity which depend on the time elapsed following drug administration.