In order to delimit the supra-brainstem structures that are activated during the sleep–waking cycle, we have examined c-fos immunoreactivity in four groups of polygraphically recorded cats killed after 3 h of prolonged waking (W), slow-wave sleep (SWS), or paradoxical sleep (PS), following microinjection of muscimol (a γ-aminobutyric acid, GABA agonist) into the periaqueductal grey matter and adjacent areas [Sastre et al. (1996), Neuroscience, 74, 415–426]. Our results demonstrate that there was a direct relationship between a significant increase in c-fos labelling and the amount of PS in the laterodorsalis tegmenti in the pons, supramamillary nucleus, septum, hippocampus, gyrus cingulate, amygdala, stria terminalis and the accumbens nuclei. Moreover, in all these structures, the number of Fos-like immunoreactive neurons in the PS group was significantly higher (three to 30-fold) than in the SWS and W groups. We suggest that the dense expression of the immediate-early gene c-fos in the rhinencephalon and striatum may be considered as a tonic component of PS at the molecular level and that, during PS, the rhinencephalon and striatum are the main targets of an excitatory system originating in the pons.