The proinflammatory cytokine interferon (IFN-γ) is an immunomodulatory molecule released by immune cells. It was originally described as an antiviral agent but can also affect functions in the nervous system including circadian activity of the principal mammalian circadian pacemaker, the suprachiasmatic nucleus. IFN-γ and the synergistically acting cytokine tumor necrosis factor-α acutely decrease spontaneous excitatory postsynaptic activity and alter spiking activity in tissue preparations of the SCN. Because IFN-γ can be released chronically during infections, the authors studied the long-term effects of IFN-γ on SCN neurons by treating dispersed rat SCN cultures with IFN-γ over a 4-week period. They analyzed the effect of the treatment on the spontaneous spiking pattern and rhythmic expression of the “clock gene,” Period 1. They found that cytokine-treated cells exhibited a lower average spiking frequency and displayed a more irregular firing pattern when compared with controls. Furthermore, long-term treatment with IFN-γ in cultures obtained from a transgenic Per1-luciferase rat significantly reduced the Per1-luc rhythm amplitude in individual SCN neurons. These results show that IFN-γ can alter the electrical properties and circadian clock gene expression in SCN neurons. The authors hypothesize that IFN-γ can modulate circadian output, which may be associated with sleep and rhythm disturbances observed in certain infections and in aging.