IL-1beta induces anorexia and adipsia. Here, we report that intracerebroventricular (ICV) pretreatment with an antisense (but not sense) phosphothio-oligodeoxynucleotide to the IL-1 receptor type I (IL-1RI, 1.28 microg or 239 pmol twice daily for 3.5 days before IL-1beta plus antisense) inhibits the anorexia, but not the adipsia induced by the ICV administration of 2.0 ng IL-1beta/rat (a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). The mean 2 h food intake decrease in response to IL-1beta was 5.6% (n = 10) in the antisense- and 43% in the sense (n = 9)-treated groups; the mean 2 h water intake decrease was 40% in the antisense- and 39% in the sense-treated groups. The intraperitoneal administration of IL-1RI antisense, in doses equivalent to those administered centrally, had no effect on the anorexic effect induced by ICV administered IL-1beta; this indicates a direct action in the central nervous system. The results suggest that: i) IL-1RI is involved in the short-term anorexigenic, but not the adipsogenic effect induced by centrally administered IL-1beta; and ii) the approach presented using antisense strategies is applicable to study the molecular basis of IL-1 mediated behaviors.