Neopentylcobalamin in neutral solution at 25 °C is stable under nitrogen but is decomposed by O₂ and by imidazole to give a cob(III)alamin and by hydrogen-atom donors such as thiols and PrⁱOH to give the cob(II) alamin and neopentane. The reaction is ascribed to reversible homolytic fission of the Co–C bond to give a low steady-state concentration of the cob(II)alamin and neopentyl radicals, which can then form neopentane by the abstraction of a hydrogen atom. Neopentylcobinamide is also decomposed by high concentrations of imidazole, while the purely five-co-ordinate neopentylcobalamin in acid and neopentylcobinamide in neutral solution are stable both in the presence and absence of O₂. Labilisation of the Co–C bond is ascribed to steric distortion around the co-ordinated C atom in the six-co-ordinate neopentyl complexes. It is suggested that neopentylcobalamin provides a model for the labilisation of the Co–C bond in the vitamin B₁₂ coenzymes, and possible mechanisms for the isomerase reactions are discussed.