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 intracerebroventricularly (i.c.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 less than 25 micrograms administered i.c.v., dose-dependently attenuated while 75 micrograms i.c.v. potentiated ethanol (i.p.)-induced motor incoordination. Similarly, caffeine less than 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 micrograms i.c.v.; less than 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.