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1 The chemoreactive ligands 5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl)-amino)-2-methylpropyl)amino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (DCITC) and 8-hydroxy-5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl)amino)-2-methylprop-2-yl)amino-1-hydroxyethyl)-carbostyril (HCITC) were synthesized and shown to be potent irreversible antagonist and agonist ligands, respectively, for the b-adrenoceptor in DDT 1 MF-2 (DDT) cells and the rat isolated aorta. 3 In the rat isolated aorta, DCITC (0.1 mM) did not a ect either the phenylephrine-mediated tissue contraction or the acetylcholine-mediated relaxation. DCITC attenuated the maximal (7)-isoprenalinemediated relaxation of a phenylephrine contracted aorta in a concentration-dependent manner and shifted the dose-response curves for (7)-isoprenaline to the right. The DCITC-induced decrease in maximal response was not reversed by extensive tissue washing. By use of the operational model of agonism, the calculated dissociation constant for (7)-isoprenaline ws 286 nM and the estimated receptor reserve for this agonist was 23% at the maximal response. 4 HCITC and (7)-isoprenaline stimulated cyclic AMP accumulation in DDT cells with pD 2 values (negative logarithm to base 10 of EC 50 ) of 7.95 and 7.97, respectively, and both mediated the same maximal stimulation. In the rat isolated aorta, HCITC produced a concentration-dependent relaxation of the tissue with a pD 2 value of 6.62, whereas the pD 2 for (7)-isoprenaline was 7.03. However, HCITC produced a greater maximal relaxation of the tissue than (7)-isoprenaline. The HCITC-mediated stimulation of cyclic AMP accumulation and relaxation of the isolated tissue were blocked when the bantagonist propranolol was added concurrently. In contrast, once the HCITC-mediated responses were established, the addition of propranolol did not result in any attenuation indicating that HCITC is an irreversible b-agonist.