The hypothalamic suprachiasmatic nuclei (SCN), the site of a mammalian circadian clock, exhibit a dense immunoreactivity for glial fibrillary acidic protein (GFAP), a specific marker for astrocytes. Although there is evidence of a circadian variation in GFAP-IR in the hamster SCN and of the participation of glial cells in input and output mechanisms of the clock, the role of these cells within the circadian system is not clearly understood. The fact that astroglia can express and respond to cytokines suggests that they could work as mediators of immune signals to the circadian system. In the present study, we have found a daily variation of GFAP-IR in the mouse SCN, peaking during the light phase. In addition, we have identified GFAP and nuclear factor-kappaB (NF-kappaB) in glial cells within the SCN and in primary cultures of the mouse SCN. Moreover, SCN glia cultures were transfected with an NF-kappaB/luc construct whose transcriptional activity was increased with lipopolysaccharide 2 mug/ml, tumor necrosis factor-alpha 20 ng/ml, or interleukin-1alpha 100 ng/ml, after 12 hr of stimulation. These results suggest that the glial cells of the SCN can mediate input signals to the mouse circadian system coming from the immune system via NF-kappaB signaling.