Adenosine receptors play an important role in learning and memory as their antagonists have been found to facilitate learning and memory in various tasks in rodents. However, few studies have examined the effect of adenosine A2A receptor deficiency on cognition. In the present study, we therefore used the Y-maze, a simple two-trial recognition test to measure spatial recognition memory in mice lacking adenosine A2A receptors. The results showed that adenosine A2A receptor knockout mice had a higher percentage of novel arm visits as first choice than wild-type CD1 mice. Moreover, these mice showed longer duration of visits in the novel arm when compared with controls, suggesting that the lack of adenosine A2A receptors improved spatial recognition memory. On the other hand, mice lacking the adenosine A2A receptors had low scores in the number of arm visits, suggesting that they were hypoactive. In conclusion, these data suggest the involvement of adenosine receptors in modulating spatial recognition memory in mice, consistent with earlier findings using adenosine receptor antagonists.