-agonists used for treatment of obstructive lung disease have a variety of different structures, but are typically classified by their intrinsic activities for stimulation of cAMP, and predictions are made concerning other downstream signals based on such a classification. We generated modified ₂-adrenergic receptors (₂AR) with insertions of energy donor and acceptor moieties to monitor agonist-promoted conformational changes of the receptor using intramolecular bioluminescence resonance energy transfer in live cells. These studies suggested unique conformations stabilized by various agonists which were not based on their classic intrinsic activities. To address the cellular consequences of these differences, G_s-coupling, G_i-coupling (p44/p42 activation), GRK-mediated receptor phosphorylation, internalization and downregulation were assessed in response to isoproterenol, albuterol, terbutaline, metaproterenol, salmeterol, formoterol and fenoterol. In virtually every case, agonists did not maintain the classic rank order, indicating that distinct signaling is evoked by -agonists of different structures which is unrelated to intrinsic activity. The extensive pleiotropy of agonist responses shown here suggests that classification of agonists by cAMP-based intrinsic activity is inadequate as it pertains to other intracellular events, and, that it may be possible to engineer a -agonist which stabilizes conformations that evoke an ideal portfolio of signals for therapeutic purposes.