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Abstract: The binding properties of the three cloned VIP/PACAP receptors and their coupling to G proteins and effectors can be studied in cells expressing each recombinant protein. The data obtained in these models must be critically evaluated:the expression of a high receptor density may reveal irrelevant receptors states and coupling to non-cognate G protein, and entail a marked amplification of the response as well as distortions in the selectivity profile of full and partial agonists. These models are, however, of great interest in the design of selective agonists and antagonists for each receptor subtype. The availability of selective ligands will facilitate the identification of the receptor subtype responsible for PACAP and VIP actions in cells and tissues.