Adenosine has been implicated in the physiological regulation of sleep propensity. The adenosine-receptor-antagonist, caffeine (100 mg), administered immediately prior to a nocturnal sleep episode, has previously been shown to lower sleep propensity as indexed by a reduced sleep efficiency, a reduced EEG power density in low delta frequencies and enhanced power density in the frequency range of sleep spindles. To further investigate the role of adenosine in sleep regulation we administered 200 mg of caffeine at 07.10 h and analyzed the sleep stages and EEG power spectra during the subsequent night in nine healthy men. Caffeine levels in saliva decreased from a maximum of 17 mumol/l one hour after intake, to 3 mumol/l immediately prior to the sleep episode starting at 23.00 h. Compared to placebo, sleep efficiency and total sleep time were significantly reduced. EEG power density in nonREM sleep was suppressed in the 0.25-0.5 Hz band and enhanced in the frequency range of sleep spindles (11.25-12.0 Hz and 13.25-14.0 Hz). In REM sleep EEG power density was suppressed in the frequency range of 0.75-4.5 and 5.25-6.0 Hz. The data indicate that a saliva level of caffeine as low as 3 mumol/l directly affects sleep propensity or, alternatively, that the presence of caffeine in the central nervous system during the waking episode reduces the progressive increase of sleep propensity associated with wakefulness.