ICI-118551 HCl, the hydrochloride salt of ICI118551, is a novel, potent and highly selective β2 adrenergic receptor antagonist, with Kis of 0.7, 49.5 and 611 nM for β2, β1 and β3 receptors, respectively. beta(2)-adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. ICI 118551 binding directs the beta(2)AR to a G(i)-coupled form and away from the G(s)-coupled form (ligand-directed trafficking). ICI 118,551 effectively acts as an agonist at the G(i)-coupled beta(2)AR, producing a direct negative inotropic effect. Conditions where beta(2)ARs are present and G(i) is raised (failing human heart, TGbeta(2) mouse heart) predispose to the appearance of the negative inotropic effect.