Two series of diastereopure phenylcyclopropylamine analogues, 2-fluoro-2-phenylcyclopropylamines and 2-fluoro-2-phenylcyclopropylalkylamines, as well as 2-fluoro-1-phenylcyclopropylamines and 2-fluoro-1-phenylcyclopropylmethylamines, were synthesized in order to study the effects of fluorine substitution on monoamine oxidase inhibition. Inhibitory activity was assayed using commercially available microbial tyramine oxidase. Characterization of tyramine oxidase, carried out prior to the inhibition experiments, confirmed earlier suggestions that this enzyme is a semicarbazide-sensitive copper-containing monoamine oxidase. The most potent competitive inhibitor was trans-2-fluoro-2-phenylcyclopropylamine, which had an IC(50) value 10 times lower than that of the nonfluorinated compound, tranylcypromine. 2-Fluoro-1-phenylcyclopropylmethylamine was found to be a weak noncompetitive inhibitor of tyramine oxidase. The presence of a free amino group, directly bonded to the cyclopropane ring, and a fluorine atom in a relationship cis to the amino group were structural features that increased tyramine oxidase inhibition.