Poly(2,5-disubstituted-1,4-phenylene ethynylene)s, PPEs. are generally synthesized by Pd-catalyzed Coupling polymerizations of appropriately substituted 1.4-diiodobenzenes and 1.4-diethynylbenzenes (i.e., condensation polymerization of A-A and B-B type monomers). If the monomers are not symmetrically substituted. this results in an irregular substitution pattern of the side chains along the polymer backbone. As with other classes of conjugated polymers, the relative placement of side chain along the backbone should influence the properties of the materials. We report a new synthetic approach to prepare regioregular unsymmetrically substituted PPEs by polymerization of 4-iodophenylacetylenes (i.e., a condensation polymerization of a single A-B type monomer). We have synthesized both the regiorandom and regioregular PPEs from unsymmetrically Substituted monomers. We provide a detailed discussion of various approaches to the synthesis of PPEs with different regioregularities and provide a preliminary description of the differences between regioregular and regiorandom analogues.