The concept that polyanaines may provide lead compounds for the development of selective ligands for different neurotransmitter receptors is discussed. Using a linear tetramine disulfide as the focus, structure-activity studies leading to different prototypes displaying selectivity for α-adrenoreceptors, M₂ muscarinic receptors and NPY receptors, respectively, are reviewed. It is shown that polyamines have receptor specificity since they are site-directed, owing to different chain lengths separating the protonable nitrogens and to the presence of those peculiar structural elements, such as disulfide bonds and aromatic substituents, which make them capable of discriminating at the binding stage. The pharmacological properties and site(s) of action of the prototypes benextramine, a tetramine disulfide with irreversible α-adrenoreceptor blocking properties, methoctramine, a tetramine displaying high affinity and high selectivity for M₂ muscarinic receptors, and CM 207-77, a diamine disulfide capable of discriminating between NPY receptors, are presented.