Interleukin-1beta (IL-1beta ) has anorectic, hyperthermic, and analgesic or hyperalgesic (depending on the studies) effects in the rat. These effects appear to be mediated by the central nervous system; however, the exact localization of action of IL-1beta in the brain has never been delineated with precision. The purpose of this study was to determine precisely where IL- IO acts in the hypothalamus and in the thalamus to modulate food intake, body temperature, and pain sensitivity. Animals were tested after local intracerebral microinjections of 5 ng of IL-1beta dissolved in 0.3 microl of saline, or of 0.3 microl saline alone. The results show that IL-1beta has anorectic effects in 3 diencephalic sites (the perifornical area, an area above the optic chiasma, and an area internal to the mamillo-thalamic tract), and not in 9 other sites tested. IL-1beta has hyperthermic effects in 7 sites (the media] and lateral preoptic area, the hypothalamic periventricular substance, the dorso-medial and arcuate nuclei of the hypothalamus, and the centro-medial and gelatinosus nuclei of the thalamus), and not in 6 other sites. IL-1beta has analgesic effects in the centro-medial and gelatinosus nuclei of the thalamus, and not in 7 other sites. IL-1beta also increases food intake and decreases pain sensation thresholds in the paraventricular nucleus of the hypothalamus. Therefore IL-1beta has very selective anatomical sites of action in the brain, and the paraventricular nucleus of the hypothalamus appears to have special properties regarding the effects of IL-1beta on food intake and pain sensation regulation.