An approach designed to elucidate structure-action relationships (SAR) for hypolipidemic agents is described. A working hypothesis is developed in support of the suggestion that a common mechanism is involved in the hypocholesteremic effects produced by certain aryloxyacetic and phenylbutyric acids. To test this hypothesis experimentally, the synthesis of a series of styrylacetic acids, structurally similar to previously prepared aryloxyacetic acids, is proposed to enable evaluation of their hypolipidemic properities. A major feature of this hypothesis is that many of the compounds designed for study will prevent metabolism by the routes shown to occur with the parent compound affording metabolites with greatly reduced activity and increased toxicity. Results obtained from in vitro tests for hypocholesteremic and antilipolytic activities and from in vivo studies should significantly aid in further efforts toward the design of safe and effective hypolipidemic agents for use in the treatment of atherosclerosis and coronary heart disease.