G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins G(s) (stimulatory) and G(i) (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and G(i) are mediated by the C-terminal helix of the G(i) alpha-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, G(i)-bound and arrestin-bound forms of rhodopsin with inactive and G(s)-bound forms of the beta(2)-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of G(s), G(i) and arrestin by activated G-protein-coupled receptors.