Interleukin-8 (IL-8) is a cytokine found in the brain. In this study, the ability of IL-8 to induce sleep in rabbits and rats was investigated. Twenty-seven Sprague-Dawley rats and 16 male New Zealand White rabbits were provided electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly (i.c.v.) with pyrogen-free saline and, one of the following doses of IL-8 on a separate day: 1.25 or 12.5 ng in rabbits and 10, 50, or 100 ng in rats. EEG, brain temperature, and motor activity were recorded for 23 h after the i.c.v. injections. IL-8 increased time spent in non-rapid eye movement sleep (NREMS) without affecting rapid eye movement sleep (REMS). In rabbits, both doses of IL-8 promoted NREMS. In rats, the 10 and 50 ng doses of IL-8 failed to affect sleep, but the 100 ng dose of IL-8 enhanced NREMS. EEG slow-wave activity during NREMS was increased after the high dose of IL-8 in rabbits. IL-8 also induced fever in rabbits but not rats. Heat inactivated IL-8 did not alter any of the parameters measured. Current results support the notion that the brain cytokine network plays a role in sleep regulation.