Immunohistochemical localization of adenosine deaminase (ADA), marker for the putative neurotransmitter/neuromodulator adenosine, has revealed a population of ADA-positive neurons in the ventrolateral hypothalamus in the rat brain. These posterior neurons possess adenosine uptake sites. We have studied the effects of local injections of adenosinergic drugs on the sleep-wake cycle in the rat. Microinjection of erythro-9-(hydroxy-2, nonyl-3) adenine (EHNA), a specific inhibitor of adenosine deaminase, resulted in a significant decrease in wakefulness (W) and an increase in deep slow wave sleep (SWS, or S2) and paradoxical sleep (SP). On the other hand, microinjections of soluflazine, a nucleoside transport inhibitor, increased W and decreased total sleep. These opposite modifications may reflect opposite variations in the extracellular concentrations of Ado and consequently different responses of A1/A2 adenosine receptors.