Abstract— The possible biphasic effect of caffeine on acute ethanol-induced motor incoordination by rotorod evaluation was investigated in mice. Caffeine in various doses was administered intracerebro-ventricularly (i.e.v.) to mice implanted with permanent indwelling stainless steel guide cannulae and intraperitoneally (i.p.) to non-cannulated animals. A motor incoordinating test dose of ethanol, 2 g kg−1, was given i.p. in both cases. Caffeine < 25 μg administered i.e.v., dose-dependently attenuated while 75 μg i.c.v. potentiated ethanol (i.p.)-induced motor incoordination. Similarly, caffeine < 20 mg kg−1 given i.p., dose-dependently attenuated while 62.5 mg kg−1 potentiated ethanol (i.p.)-induced motor incoordination. The data obtained demonstrated that caffeine given either i.c.v. or i.p. exerted biphasic effects on ethanol-induced motor incoordination. The data also suggested that caffeine antagonized ethanol-induced motor incoordination when administered in appropriately low concentrations. At these low concentrations (< 25 μg i.c.v.; < 20 mg kg−1 i.p.) caffeine is well known to display high affinity for adenosine binding sites. Therefore, the present investigation lends further support to our earlier suggestion that adenosine may be involved in the motor impairing effect of ethanol.