Aromatic amine dehydrogenase (AADH) is the second enzyme known to possess the tryptophan tryptophylquinone (TTQ) prosthetic group. Its ability to catalyze the oxidative deamination of a wide range of aromatic and aliphatic amines has been investigated. Steady-state and transient kinetic studies of the reaction of AADH with a series of p-substituted phenylethylamines were performed to determine structure-reactivity correlations. The Km values correlated strongly with hydrophobic effects. The microscopic rate constant associated with TTQ reduction, k3, correlated with electronic substituent effects, particularly field/inductive effects, in a manner consistent with the formation of a carbanionic reaction intermediate in the reductive half-reaction. Transient kinetic studies were also performed with a series of p-substituted benzylamines, which were not substrates in the steady-state assay, but which did stoichiometrically reduce TTQ. The k3 for the reaction with benzylamines also correlated well with electronic effects. The rate constant associated with the release of the aldehyde product was also determined for the phenylethylamines and appears to be the most rate-limiting step in the overall oxidation-reduction reaction. This rate constant correlated with hydrophobic amines. This substrate specificity for aliphatic amines is opposite of that of methylamine dehydrogenase (MADH), the other known TTQ enzyme. On the basis of these studies, a reaction mechanism is proposed for AADH. These data are discussed in relation to the results of structure-reactivity correlation studies of the reactions catalyzed by MADH and two eukaryotic quinoproteins with different quinone prosthetic groups, plasma amine oxidase and lysyl oxidase.