Ab initio molecular orbital theory is used to investigate several possible mechanisms involving free radical intermediates for the coenzyme- B12-dependent rearrangement catalyzed by methylmalonyl-CoA mutase. Our calculations suggest that an intermolecular pathway in which transient fragmentation of the substrate-derived radical is followed by recombination of the fragments ('fragmentation-recombination') is unlikely, but not out of the question. An alternative intramolecular pathway ('addition-elimination') is found to be energetically more favorable. Protonation of the species involved in this latter pathway is found to further reduce the barrier for rearrangement. Examination of the middle ground between the protonated and unprotonated intramolecular mechanisms reveals a continuous spectrum of behavior and demonstrates the potential importance of partial proton transfer. Support for this proposal is obtained from the X-ray crystal structure of the protein. The stereochemistry of the rearrangement has also been examined and leads to a new proposal consistent with experiment.