High-throughput experimentation (HTE) was successfully applied in atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) for the rapid screening and optimization of different reaction conditions. A library of 108 different reactions was designed for this purpose, which used four different initiators [ethyl 2-bromoisobutyrate, methyl 2-bromopropionate, (1-bromoethyl)benzene, and p-toluenesulfonyl chloride], five metal salts (CuBr, CuCl, CuSCN, FeBr2, and FeCl2), and nine ligands (2,2'-bipyridine and its derivatives). The optimal reaction conditions for Cu(I) halide, CuSCN, and Fe(II) halide-mediated ATRP systems with 2,2'-bipyridine and its 4,4'-dialkyl-substituted derivatives as ligands were determined. Cu(I)-mediated systems were better controlled than Fe(II)-mediated ones under the examined conditions. A bipyridine-type ligand with a critical length of the substituted alkyl group (i.e., 4,4'-dihexyl 2,2'-bipyridine) exhibited the best performance in Cu(I)-mediated systems, and p-toluenesulfonyl chloride and ethyl 2-bromoisobutyrate could effectively initiate Cu(I)-mediated ATRP of MMA, resulting in polymers with low polydispersities in most cases. Besides, Cu(I) halide-mediated ATRP with 4,5'-dimethyl 2,2'-bipyridine as the ligand and p-toluenesulfonyl chloride as the initiator proved to be better controlled than those with 4,4'-dimethyl 2,2'-bipyridine as the ligand, and polymers with much lower polydispersities were obtained in the former cases. This successful HTE example opens up a way to significantly accelerate the development of new catalytic systems for ATRP and to improve the understanding of structure-property relationships of the reaction systems. (C) 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1876-1885, 2004.