Ever since the initial discovery of the structurally homologous G-protein-coupled receptors, the search has been ongoing for identifying suitable expression systems. Such systems should be easy to use, inexpensive, and appropriate for mass production. In addition, these systems should permit analysis of function, including ligand binding and G-protein-regulated effector activation. Although expression in Escherichia coli (see Chapter 14) provides several of these features, only eukaryotic cells contain the appropriate complement of endogenous G-proteins and effectors to study second messenger activation. Mammalian cell culture remains expensive, is not amenable to large-scale amplification, is prone to infection by contaminant microorganisms, and can undergo loss of receptor-bearing plasmids.