The molecular mechanisms involved in sleep regulation and function are largely unknown, and our understanding of the localization of such mechanisms within specific brain structures is still incomplete. In this work, we explored the consequences of sleep deprivation by the immunocytochemical mapping of the induction of the protein product of the immediate early gene c-fos in the brain of sleep-deprived rats. The expression of Fos protein is an indicator of neuronal activity. In addition, since immediate early genes can function as "third messengers" and regulate the transcription of a number of target genes, their induction could be directly relevant to the homeostasis and functions of sleep. The present results show that, as a result of 24 hours of manual sleep deprivation, Fos-like immunoreactive cells are found in specific brain areas. These areas include the medial preoptic area of the hypothalamus, the nucleus accumbens, the lateral septum, several regions of the dorsal pontine tegmentum (central gray, dorsal raphe, locus coeruleus, pedunculopontine and laterodorsal tegmental nuclei, parabrachial nuclei) and an area medial to the parabigeminal nucleus at the ponto-mesencephalic junction. Some of these areas had already been implicated in slow-wave sleep and desynchronized sleep regulation.