The exceptionally good monoamine oxidase (MAO) substrate properties of several 4-(arylmethyl)-1-methyl-1,2,3,6-tetrahydropyridine derivatives related to the neurotoxin MPTP have prompted studies to evaluate the corresponding properties of tetrahydropyridine derivatives bearing heteroatom-linked groups at C-4. The expected dihydropyridinium metabolites generated from these MAO-A- and MAO-B-catalyzed oxidations of the 4-(aryloxy)tetrahydropyridine analogs were found to undergo rapid hydrolytic cleavage to yield the corresponding arenol and 1-methyl-2,3-dihydro-4-pyridone, a species that could be monitored spectrophotometrically. We have exploited this reaction sequence to probe the active sites of beef liver MAO-B and human placental MAO-A with a variety of 4-(aryloxy)-1-methyl-1,2,3,6-tetrahydropyridine derivatives. The results are discussed in relationship to recently published reports describing the MAO-A vs MAO-B selectivity of various 4-(arylmethyl)tetrahydropyridine derivatives.