Modafinil is a wakefulness-promoting substance whose profile differs from that of the classical psychostimulants. It is still unknown whether waking induced by modafinil and wakefulness induced by sleep deprivation differ in terms of their effect on subsequent sleep. To investigate this problem sleep was recorded in two groups of OF1 mice. One group received modafinil (200 mg/kg, i.p.) at light onset which induced a period of wakefulness of approx. 5 h, while animals of the subsequent control group were injected with vehicle and kept awake for an equivalent duration. The effect of the two treatments on sleep was similar. REM sleep was initially reduced and slow-wave activity (SWA; EEG power in the 0.75-4.0 Hz range) in nonREM sleep was enhanced for several hours. The SWA increase was more prominent over the frontal cortex than over the occipital cortex after both treatments. A minor difference was seen at the occipital site where the initial rise of power in the low-frequency range was larger after vehicle combined with enforced waking than after modafinil. The study shows that the homeostatic sleep response following the modafinil-induced wakefulness corresponds largely to the response following a non-pharmacologically induced extended waking episode.