It is emphasised that free energy changes represent the difference between two states. Intramolecular reactions often proceed at a rate faster than the analogous intermolecular reaction because of the greater entropy of the initial state of the intermolecular reaction. This rate enhancement can be increased if strain in the initial state is relieved in the transition state, or be decreased if strain energy is increased in the transition state of the intramolecular reaction. Binding energies between enzymes and substrates represent energy differences between initial and final states. The specificity of enzyme-catalysed reactions depends on differences between initial and transition states. Solvation effects on specificity are initial state and not transition state effects in the α-chymotrypsin-catalysed hydrolysis of 4-nitrophenyl acetate and N-acetyl-L-tryptophan methyl ester.