Interleukin-1β (IL-1β) is a well characterized sleep regulatory substance. To study receptor mechanisms for the sleep-promoting effects of IL-1β, sleep patterns were determined in control and IL-1 type I receptor knockout (IL-1RI KO) mice with a B6x129 background after intraperitoneal injections of saline or murine recombinant IL-1β. The IL-1RI KO mice had slightly but significantly less sleep during the dark period compared with the controls. IL-1β dose dependently increased non-rapid eye movement sleep (NREMS) and suppressed rapid eye movement sleep (REMS) in the controls. The IL-1RI KO mice did not respond to IL-1β. In contrast, the IL-1RI KO mice increased NREMS and decreased REMS after administration of tumor necrosis factor-α (TNF-α), another well characterized sleep-promoting substance. These results 1) provide further evidence that IL-1β is involved in sleep regulation, 2) indicate that the effects of IL-1β on sleep are mediated by the type I receptor, and 3) suggest that TNF-α is capable of inducing sleep without the involvement of IL-1.