The present study examined the effect of ethanol (0.25-1.0 g/kg, I.P.) alone and in combination with drugs affecting different ligand-gated ion channels on a horizontal locomotor activity of male Wistar rats. None of the drugs given alone affected the locomotor activity. Similarly, combining ethanol either with nicotine (0.1 or 0.6 mg/kg, S.C.) or the competitive NMDA receptor antagonist, CGP 40116 (0.5 mg/kg, I.P.) did not result in any significant changes in ambulation. On the other hand, a significant hyperadditive interaction between ethanol (0.5 or 1.0 g/kg) and the uncompetitive NMDA receptor antagonist, dizocilpine (0.1 mg/kg, I.P.) was found. Thus, a combined administration of ethanol and dizocilpine produced a marked stimulation of the locomotor activity. Combining 1.0 g/kg ethanol with the 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide (5.0 mg/kg, I.P.) tended to produce locomotor stimulation. Our results suggest the existence of interaction between ethanol and the NMDA receptor complex in mediation of locomotor stimulation. Alternatively, a common neurotransmitter system (other than glutamatergic) mediate central stimulatory effects of ethanol and dizocilpine. A possible role of dopamine in this interaction is being discussed.