There is evidence that adenosine may participate in the regulation of sleep and wakefulness in the mammalian central nervous system. To understand whether the adenosine receptor subtypes, A, and A > , . , , are involved in the modulation of sleep and waking, we carried out electroencephalographic (EEG) studies in the rat using selective agonists and antagonists for either receptor. EEG activity was recorded for 6 h after intraperitoneal administration of drugs, and the stages of wakefulness, rapid eye movements (REM) sleep and non-REM sleep were classified thereafter. The dose-response effects of the A, agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), and the A , , agonist, 2-hexynyl-5'-N-ethylcarboxamido-adenosine (2HE-NECA), were examined. Both drugs, CCPA (0.003-0.03 mgikg) and 2HE-NECA (0.03-0.3 mg/kg), given at a dose range known to be effective pharmacologically did not significantly modify the sleep patterns in the whole recording period. We have also studied the effects of the selective A, antagonist, 8-cyclopentyl-I ,3-dipropylxanthyne (DPCPX), and the A , , antagonist, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-l4J-cl-I ,2,4,-triazolo-[I,5-~]-pyrimidine (SCH 58261 j. The results obtained with antagonists were compared with those of two non-selective adenosine antagonists, caffeine (10 mgikg) and 9-chloro-2-(2-furyl)-5,6-dihydro-[l,2,4]-triazolo-[l,5-c]-quinazolin-5-imine (CGS 15943). Like caffeine, both CGS 15943 (0.3-10 mg/kg) and SCH 58261 (0.3-10 mg/kg), at the highest dose, increased wakefulness, while DPCPX (0.3-10 mgikg) did not affect sleep parameters. The data indicate that potent and selective adenosine agonists have little or no effect on sleep states in the rat, while using adenosine antagonists it seems that A , , receptors are primarily involved in the modulation of wakefulness.