We propose that the inhibitory neuromodulator adenosine may underlie the findings of this study. Adenosine inhibits excitatory neurotransmission and overall neuronal activity by acting on adenosine A1 receptors, which are widely distributed in the mammalian brain (2). Adenosine’s pivotal role in sleep modulation is strongly supported by the subjective and EEG-defined arousal produced by its antagonists, caffeine and theophylline, as well as by the fact that extracellular adenosine concentration is linked to neuronal metabolic activity (3). Regarding sleep deprivation specifically, it is noteworthy that 1) adenosine levels progressively increase after sustained, prolonged wakefulness in cats (3), 2) A1 receptor agonists mimic the electroencephalographic effects of sleep deprivation in rats (4), and 3) caffeine suppresses recovery sleep after deprivation (3). Therefore, the reduced metabolic rates observed in responders after sleep deprivation (1) are consistent with neuronal inhibition secondary to increases in extracellular adenosine. In addition, higher baseline metabolic rates in these patients may reflect a deficient adenosinergic inhibitory tone.