Adenosine accumulates in the basal forebrain during prolonged wakefulness and induces sleep. There is abundant evidence showing that the sleep-inducing effects are mediated locally in the basal forebrain through the adenosine A1 receptor. In previous studies an increase in the mRNA expression but no apparent change in the ligand binding of the A1 receptors have been found. In the present study we used [(35)S]GTPgammaS autoradiography to assess regional A1 receptor dependent G-protein activity in rat brain during prolonged wakefulness and recovery sleep. We found that the G-protein activity was increased in the cortex but not in the basal forebrain during the first hours of sleep deprivation, suggesting different A1 receptor mediated responses to increasing adenosine concentrations in different brain areas.