Pretreatment to guinea pigs with sc isoprenaline (Iso) 10 micrograms/kg tid x 7 d reduced the effect of Iso on protecting histamine-induced asthma and decreased its pD2 values in relaxing isolated tracheal strip. This treatment did not change the asthmatic effect induced by histamine and the effect of Iso on positive chronotropic action, but elevated the blood pressure. These results suggest that it is easier to develop the tolerance of beta 2-adrenoceptors of respiratory smooth muscles than that of beta 1-adrenoceptors of heart. Radioligand binding assay showed that the treatment decreased the number of binding sites of beta-adrenoceptors on lungs of guinea pigs but did not change the binding affinity.