The kinetics of the thermal Co-C bond homolysis of the complexes of a vitamin B-12 binding protein (haptocorrin) with a series of analogs of neopentylcobalamin modified in side chain structure have been studied. The analogs include the C13 epimer in which the e propionamide side chain adopts an "upwardly" axial conformation and a series of c side chain-modified analogs, including the c-monocarboxylate, the c-N-methylamide, the c-N,N-dimethylamide, and the c-N-isopropylamide. Activation parameters for the thermal homolysis of these complexes show that the previously observed stabilization of alkylcobalamins by haptocorrin is due to both enthalpic and entropic factors. With the exception of that for the analog having the bulkiest c side chain substituent; neopentylcobalamin-c-N-isopropylamide, the enthalpies of activation are independent of analog structure, but the entropies of activation increase with the steric bulk of the c side chain and with the number of "upwardly" projecting side chains, as previously observed for protein-free neopentylcobalamin and its analogs. The results are discussed in terms of the solvent cage effect on Co-C bond homolysis and the importance of corrin ring side chain thermal motions to the entropy of activation for this reaction.