To identify key parameters which influence the efficiency of nonenzymatic template-directed oligonucleotide reactions, a kinetic study of oligoguanylate synthesis on a polycytidylate (poly(C)) template has been performed. This oligomerization is satisfactorily described by three kinetic processes: (i) dimerization to form the first primer (k(2)), (ii) elongation of a preformed primer (k(i), i greater than or equal to 3), and(iii) hydrolysis of the monomer to form deactivated material (k(h)), with k(h) < k(2) < k(i). This is the first reported study that includes rate determinations of ki as a function of the concentration of both poly(C) template and the activated monomer, guanosine 5'-monophosphate-2-methylimidazolide (2-MeImpG), in the range 2 mM less than or equal to [poly(C)] less than or equal to 50 mM and 5 mM less than or equal to [2-MeImpG] less than or equal to 50 mM. k(i) values determined under conditions where the template is fully saturated with monomer are practically independent of both monomer and polymer concentration and thus strongly support a template-directed elongation model. Values of k(i) determined with a partially occupied template support a mechanism wherein the reaction of the oligonucleotide primer with a template-bound monomer is assisted by the presence of two additional downstream template-bound 2-MeImpG molecules. Comparison between the kinetic parameters obtained here and the- ones determined in the montmorillonite-catalyzed oligoadenylate polymerization allows the proposition that the ratio of the rate constants k(i)/k(h) determines efficiency and the ratio k(i)/k(2) determines the degree or extent of a polymerization. These conclusions provide new design principles for the optimization of nonenzymatic polymerizations.