Intravenous meperidine is commonly used to treat rigors and chills in febrile patients, though its mechanism of action is unknown. Therefore a laboratory model of pyrogen-induced fever was used to evaluate the effects of meperidine on the febrile response of rats injected with bacterial endotoxin or IL-1α. Fever was measured using a computerized biotelemetry system forthe continuous monitoring of body temperature. Injection of meperidine blocked the onset of fever in rats injected with endotoxin and attenuated the febrile response in rats injected with IL-1β. Futhermore, incubation of human mononuclear leukocytes (MNL) in the presence of meperidine significantly reduced endotoxin-induced secretion of IL-1β in vitro. These data suggest that meperidine decreases rigors and chills by decreasing the “set point” for fever, perhaps by reducing MNL secretion of IL-1β.