The cholinergic agonist carbachol (1.1 mM) and the adenosinergic agonist cyclohexyladenosine (0.1 mM) were microinjected (60 nl) into the region of the caudal, oral pontine reticular formation of the rat. Local intracerebral infusion of each receptor agonist resulted in significant, long-lasting (at least 8 h) elevations in rapid eye movement sleep without reduction in latency to onset. The effects of carbachol were reduced by the muscarinic receptor antagonist atropine, while those of cyclohexyladenosine were reduced by the adenosinergic receptor antagonist 8-cyclopentyltheophylline. Atropine failed to antagonize the long-term induction of rapid eye movement sleep following cyclohexyladenosine, but did appear to suppress increases in the first 2 h. Similarity of effects on sleep parameters and the lack of additivity when injected consecutively are consistent with these agonist ligands targeting the same cellular mechanisms through their respective receptors. These findings suggest that transitory increases in the pons of either acetylcholine or adenosine may underlie long-lasting elevations in the amount of rapid eye movement sleep. Adenosine may play a role in the increased rapid eye movement sleep following prolonged wakefulness, as well as following conditions of stress and learning.