In the present study, we demonstrate that the Ca2+-inhibitable adenylyl cyclase (AC) activity in the striatum exhibits a daily oscillation with a peak occurring around 10:00 h. A circadian fluctuation of the AC activity evoked by an A2a adenosine-selective agonist was also observed. Intrastriatal injection of an A2a-selective adenosine agonist or antagonist during the interval in which the Ca2+-inhibitable AC activity was at its peak resulted in a more significant alteration of locomotor activity than those observed at a later interval. The marked circadian variation in the Ca2+-inhibitable AC activity in the striatum appears to cause a circadian fluctuation in the action of at least one neuromodulator.