Adenosylcobinamide (AdoCbi(+)) plus the sterically hindered bases 1,2-dimethylimidazole, 2-methylpyridine, and 2,6-dimethylpyridine, as well as control experiments with imidazolate and 4-methylimidazolate, have been investigated to provide chemical precedent for the benzimidazole base-off, protein histidine imidazole base-on form of adenosylcobalamin (AdoCbl, also coenzyme Bit). This imidazole base-on form of AdoCbl was observed in the recent X-ray crystallographic structural study of methylmalonyl-CoA (MMCoA) mutase; of interest to the present work is the fact that MMCoA mutase contains a long, ca. 2.5 Angstrom, Co-N(imidazole) axial bond, at least in the enzyme's crystallographically characterized Co-II/Co-III state and conformation. In the present studies, upper limits for the axial-base binding K-assoc parameters to form [AdoCbi.bulky base](+) BF4- have been obtained; these thermodynamic studies reveal that sterically hindered bases do not bind detectably to AdoCbi(+) in the ground state, which results in negligible ground-state free-energy stabilization via the formation of [AdoCbi.bulky base](+). The sterically hindered bases do, however, bind to Co(II)Cbi(+), a good energetic model of the [Ado.- - -.CoCbi](+) homolysis transition state. Kinetic studies demonstrate that the sterically hindered bases are involved in the rate-determining step of Co-C bond homolysis, accelerating it by 200-fold; hence, Co-C cleavage does occur via the low-level and otherwise nondetectable amount of [AdoCbi.bulky base](+) formed in solution. Product studies reveal (i) that both Co-C heterolysis and homolysis occur, and (ii) that there is no simple correlation between the ratio of Co-C heterolysis to homolysis and the Co-N(axial-base) bond length. Overall, the results provide strong evidence for the dominance of axial-base transition-state effects on Co-C bond cleavage, and reveal a subtle interplay of sigma and pi effects as a function of the Co-N(axial-base) bond length.