The G-protein coupled seven transmembrane domain receptors bind a wide variety of ligands of different molecular size ranging from small monoamines to large neuropeptides and peptide hormones. This review summarises data from studies on the localisation of the binding site for a few neuropeptides in their receptors and compares this to the binding pockets for non peptide ligands. The main conclusion is that neuropeptide binding involves residues on the top of several transmembrane domains and in extracellular loops of the receptors while the non peptide type ligands to the same receptors tend to bind deeper in the plane of the membrane, between several transmembrane domains--similarly to monoamines. Thus the antagonism exerted by most of the non peptide type ligands is an allosteric phenomenon whereby binding of these to another site than the peptide binding site stablises a "non agonist" binding, and for signalling inactive, conformation of the 7 TM receptor.