AGONIST-BOUND receptors activate heterotrimeric (αβγ) G proteins by catalysing replacement of GDP bound to the α-subunit by GTP^1–5. Mutations in the C terminus of the α-subunit^6,7, its covalent modification by pertussis toxin-catalysed ribosylation of ADP⁸, peptide-specific antibodies directed against it^9–11, and peptides mimicking C-terminal sequences¹², all inhibit receptor-mediated activation of G proteins. The logical prediction—that specific amino-acid residues at the C-termini of α-subunits can determine the abilities of individual G proteins to discriminate among specific subsets of receptors—has so far not been tested experimentally. Different hormone receptors specifically activate G_q or G_i whose α-subunits (α_q or α_i) stimulate phosphatidylinositol-specific phospholipase C or inhibit adenylyl cyclase, respectively^1–5. Here we replace C-terminal amino acids of α_q with the corresponding residues of α_i2 to create α_q/α_i2 chimaeras that can mediate stimulation of phospholipase C by receptors otherwise coupled exclusively to Gj. A minimum of three a_i2 amino acids, including a glycine three residues from the C terminus, suffices to switch the receptor specificity of the α_q/α_i2 chimaeras. We propose that a C-terminal turn, centred on this glycine, plays an important part in specifying receptor interactions of G proteins in the G_i/G₀/G_z family.