Methyl substituents at C-C bonds influence hydrogenolysis rates and selectivities of acyclic and cyclic C-2-C-8 alkanes on Ir, Rh, Ru, and Pt catalysts. C-C cleavage transition states form via equilibrated dehydrogenation steps that replace several C H bonds with C-metal bonds, desorb H atoms (H*) from saturated surfaces, and form lambda H-2(g) molecules. Activation enthalpies (Delta H-double dagger) and entropies (Delta S-double dagger) and lambda values for C-3-C-x cleavage are larger than for C-2-C-2 or C-2-C-1 bonds, irrespective of the composition of metal clusters or the cyclic/acyclic structure of the reactants. C-3-C-x bonds cleave through alpha,beta,gamma- or alpha,beta,gamma,delta-bound transition states, as indicated by the agreement between measured activation entropies and those estimated for such structures using statistical mechanics. In contrast, less substituted C-C bonds involve alpha,beta-bound species with each C atom bound to several surface atoms. These alpha,beta configurations weaken C-C bonds through back-donation to antibonding orbitals, but such configurations cannot form with C-3 atoms, which have one C-H bond and thus can form only one C M bond. C-3-C-x cleavage involves attachment of other C atoms, which requires endothermic C-H activation and H* desorption steps that lead to larger Delta H-double dagger values but also larger Delta S-double dagger values (by forming more H-2(g)) than for C-2-C-2 and C-2-C-1 bonds, irrespective of alkane size (C-2-C-8) or cyclic/acyclic structure. These data and their mechanistic interpretation indicate that low temperatures and high H-2 pressures favor cleavage of less substituted C-C bonds and form more highly branched products from cyclic and acyclic alkanes. Such interpretations and catalytic consequences of substitution seem also relevant to C-X cleavage (X = S, N, O) in desulfurization, denitrogenation, and deoxygenation reactions.