Mice implanted with chronic indwelling cannulas were injected in the lateral cerebral ventricle with a series of adenosine analogs and the effects on spontaneous locomotor activity were recorded. All analogs produced dose-related decreases in locomotor activity. The relative order of potency for locomotor depression was: NECA much greater than L-PIA greater than CADO greater than D-PIA. Caffeine at the lowest dose produced a significant decrease in locomotor activity. At higher doses caffeine had no effect on locomotor activity but it did antagonize the depressant effects of NECA, a finding consistent with the notion that the central stimulant action of methylxanthines is due to their antagonism of central adenosine receptors.