This article describes a rationale and strategy for the design of low molecular weight, non-peptide ligands (peptoids), using the chemical structure of mammalian neuropeptides as a starting point. These peptoids may act as either agonists or antagonists at neuropeptide receptors. As they are non-peptides, they can serve as robust tools to help establish the role of the peptides in models of physiological and pathophysiological processes and indeed they may emerge as therapeutic agents in their own right. The strategy is exemplified by the first rational design of 'peptoid' ligands for cholecystokinin (CCK) and tachykinin receptors.