G-protein coupled receptors (GPCRs) are integral membrane proteins that transduce extracellular stimuli into intracellular responses. GPCRs are allosteric machines that sample multiple conformations existing in equilibrium. Agonist binding shifts the equilibrium to active states to promote G protein signaling1. Recent crystal structures give us snapshots of inactive and active states, but not the dynamics that underlie GPCR activation. Here, we labeled six methionines on a thermostabilised a1A-adrenergic receptor2(a1A-AR) with 13CH3-Methionine to probe how different ligands modulate the conformational equilibrium of this GPCR using Nucleus Magnetic Resonance spectroscopy (NMR). Each methionine signal in 1H, 13C-HMQC NMR spectra was assigned through single site mutagenesis. Met292 sits in the orthosteric ligand binding pocket and its chemical shift was unique upon binding each ligand. Met203 on-the-other-hand, is located on the intracellular side of the receptor where G proteins interact. We found the resonance of Met203 shifts upfield in the presence of inverse agonists and the chemical shift change correlates well with inhibition efficacy (R2=0.99). The chemical shift of Met203 upon binding a less well characterized ligand of a1AAR, conotoxin τ-TIa, indicated that τ-TIa was an inverse agonist. Interestingly, the Met203 resonance shifted in an opposite direction upon agonist binding and this shift was attenuated by mutating a receptor residue known to facilitate agonist activation of the receptor. In conclusion, this study validates the current conformational equilibrium-based hypothesis of GPCR function and establishes NMR as a means to characterize the mode of action of novel GPCR ligands.