A method of producing a mutant GPCR with increased conformational stability under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, relative to its parent GPCR, the method comprising: (a) identifying in the amino acid sequence of one or more mutants of a first parent GPCR with increased conformational stability under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, relative to the first parent GPCR, the position or positions at which the one or more mutants have at least one different amino acid residue compared to the first parent GPCR, and (b) making one or more mutations in the amino acid sequence that defines a second GPCR at the corresponding position or positions, to provide one or more mutants of a second parent GPCR with increased conformational stability relative to the second parent GPCR; wherein the second parent GPCR (i) has at least 20% sequence identity with the first parent GPCR; (ii) is able to be aligned with the first parent GPCR such that the corresponding position or positions can be identified by alignment; and (iii) is of the same GPCR class or family as the first parent GPCR; and wherein prior to step (a) the one or more mutants of the first parent GPCR are obtained by a method comprising (i) providing one or more mutants of a parent GPCR, (ii) selecting a ligand of a particular class, the ligand being one which binds to the parent GPCR when the GPCR is residing in a particular conformation, (iii) determining whether the or each mutant GPCR has increased conformational stability with respect to binding the selected ligand compared to the conformational stability of the parent GPCR with respect to binding that ligand, by measuring denaturation as manifest by loss of ligand binding ability, under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, and (iv) selecting those mutants that have an increased conformational stability compared to the parent GPCR with respect to binding the selected ligand; wherein the particular conformation in which the GPCR resides in step (iii) corresponds to the same class of ligand as the ligand selected in step (ii). (a) identifying in the amino acid sequence of one or more mutants of a first parent GPCR with increased conformational stability under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, relative to the first parent GPCR, the position or positions at which the one or more mutants have at least one different amino acid residue compared to the first parent GPCR, and (b) making one or more mutations in the amino acid sequence that defines a second GPCR at the corresponding position or positions, to provide one or more mutants of a second parent GPCR with increased conformational stability relative to the second parent GPCR; wherein the second parent GPCR (i) has at least 20% sequence identity with the first parent GPCR; (ii) is able to be aligned with the first parent GPCR such that the corresponding position or positions can be identified by alignment; and (iii) is of the same GPCR class or family as the first parent GPCR; and wherein prior to step (a) the one or more mutants of the first parent GPCR are obtained by a method comprising (i) providing one or more mutants of a parent GPCR, (ii) selecting a ligand of a particular class, the ligand being one which binds to the parent GPCR when the GPCR is residing in a particular conformation, (iii) determining whether the or each mutant GPCR has increased conformational stability with respect to binding the selected ligand compared to the conformational stability of the parent GPCR with respect to binding that ligand, by measuring denaturation as manifest by loss of ligand binding ability, under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, and (iv) selecting those mutants that have an increased conformational stability compared to the parent GPCR with respect to binding the selected ligand; wherein the particular conformation in which the GPCR resides in step (iii) corresponds to the same class of ligand as the ligand selected in step (ii). (i) providing one or more mutants of a parent GPCR, (ii) selecting a ligand of a particular class, the ligand being one which binds to the parent GPCR when the GPCR is residing in a particular conformation, (iii) determining whether the or each mutant GPCR has increased conformational stability with respect to binding the selected ligand compared to the conformational stability of the parent GPCR with respect to binding that ligand, by measuring denaturation as manifest by loss of ligand binding ability, under denaturing conditions such as heat, a detergent, a chaotropic agent or an extreme of pH, and (iv) selecting those mutants that have an increased conformational stability compared to the parent GPCR with respect to binding the selected ligand; wherein the particular conformation in which the GPCR resides in step (iii) corresponds to the same class of ligand as the ligand selected in step (ii).