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G protein‐coupled receptors (GPCRs) have key roles in cell–cell communication. Recent data suggest that these receptors can form large complexes, a possibility expected to expand the complexity of this regulatory system. Among the brain GPCRs, the heterodimeric GABA_B receptor is one of the most abundant, being distributed in most brain regions, on either pre‐ or post‐synaptic elements. Here, using specific antibodies labelled with time‐resolved FRET compatible fluorophores, we provide evidence that the heterodimeric GABA_B receptor can form higher‐ordered oligomers in the brain, as suggested by the close proximity of the GABA_B1 subunits. Destabilizing the oligomers using a competitor or a GABA_B1 mutant revealed different G protein coupling efficiencies depending on the oligomeric state of the receptor. By examining, in heterologous system, the G protein coupling properties of such GABA_B receptor …