Airway inflammation may cause alteration of airway responses in chronic airway diseases, such as bronchial asthma. The objective of this study was to examine whether interleukin-1beta (IL-1beta) [corrected], one of the pro-inflammatory cytokines, has a direct effect on airway functions. The effects of IL-1beta on carbachol, KCl and isoproterenol (ISO) responses of isolated guinea-pig tracheal strips were examined by measuring isometric tension in tissue bath. Responses of tracheal strips with or without epithelium to each agonist were compared before and after incubation with IL-1beta (25 ng or 250 ng/mL). Both 1 h and 5 h incubation of the strips with 250 ng/mL IL-1beta significantly decreased the sensitivity not only to KCl (P < 0.05; P < 0.01, respectively), but also to ISO (both P < 0.05) without affecting maximum contraction or relaxation. Response to carbachol was not affected by IL-1beta. Epithelial denudation abolished the effects of IL-1beta on KCl and ISO responses. Indomethacin (2 micromol/L) [corrected] reversed the effects of IL-1beta both on KCl and on ISO. These results suggest that IL-1 beta decreases the sensitivity of airway strips to KCl and ISO, possibly by stimulating prostaglandin production from the airway epithelium [corrected].