Previous work from these laboratories has shown that the success of alkoxyamine-initiated living radical polymerization (polydispersity of product, rate of polymerization) is critically dependent on the rate of homolysis of the C-O bond of the alkoxyamine initiator. Half-lives for a range of alkoxyamines based on initiator-derived radicals or low molecular weight propagating species have been measured experimentally. The values show a marked dependence on the structure of both the nitroxide and radical components. In this work, we demonstrate that semiempirical molecular orbital calculations provide a reliable, though qualitative, prediction of the experimentally observed trends in alkoxyamine homolysis rates. For example, for a series of alkoxyamines based on nitroxides (R(CH3)(2)C)(2)NO ., C-O bond dissociation energies are predicted to decrease with an increase in ring size or the C-N-C angle (i.e., 5-membered > 6-membered > open chain > 7-membered), which is in accord with experimental results (5-membered > 6-membered > open chain). More importantly, calculations allow an assessment of the relative importance of steric and polar factors and radical stability in determining the order of alkoxyamine homolysis rates. In the case of secondary and tertiary alkoxyamines, steric factors appear to be the dominant influence. The calculations have application in the design of new initiators for living radical polymerization.