Regioselectivity is used to determine the absolute energetic differences for four different reactions catalyzed by P450. Abstraction of a hydrogen from a benzylic carbon containing a chlorine has a 1.0 kcal/mol lower barrier than abstraction from a simple benzylic carbon, which in turn is 0.4 to 0.9 kcal/mol lower than abstraction from the methyl group of an aromatic ether and 0.1 to 0.6 kcal/mol easier than aromatic hydroxylation. Isotope effects are used to determine if the enzyme-substrate complexes leading to each product, from a given substrate, are in rapid equilibrium. For all enzymes isotopically sensitive branching is observed from the benzylic carbon upon deuterium incorporation at that position to each of the other positions, indicating that each product arises from the same active oxygen species. The energetic differences determined experimentally are accurately reproduced by theoretical hydrogen atom abstractions at both the AM1 semiempirical and DFT levels of theory.