The direct aims of the proposed investigation are the elucidation of the mechanism for squalene biosynthesis from farnesyl pyrophosphate and the development of specific inhibitors of this transformation. The results of these studies are not only of fundamental significance but are potentially important to the treatment of cardiovascular diseases. The experimental approach to these goals involves the use of synthetic substrate analogues designed to interfere with the normal course of the reaction sequence, thereby revealing mechanistic details and/or inhibiting the enzyme.