1. Twelve oxygen and sulphur azaheterocycles were studied as potential substrates of rabbit liver aldehyde oxidase. Only benzoxazole and 1,2-benzisoxazole were found to be substrates.2. Nine of the compounds inhibited the oxidation of quinazoline by aldehyde oxidase and in all cases mixed inhibition kinetics were observed.3.π-Excessive heterocycles consisting of a single 5- or 6-membered ring (thiazole, oxazole) were neither substrates or inhibitors. Addition of a carbocyclic ring (benzothiazole, benzoxazole, 1,2-benzisoxazole) allowed binding to the enzyme as a substrate and/or inhibitor.4. The mixed inhibition exhibited by theπ-excessive azaheterocycles benzothiazole, 1,2-benzisoxazole, and 2-substituted benzoxazoles was characterised by aKi/KIratio greater than 1 0, whereKiis the inhibitor constant for binding to the free enzyme andKIis the inhibitor constant for binding to the ES complex. In contrast, fiveπ-deficient methyl-substituted quinolines, which are known substrates for aldehyde oxidase, exhibited aKi/KIratio of less than 1·0.5. Theπ-excessive heterocycles 2,3-benzthiophene and 2,3-benzfuran, which do not contain a nitrogen atom, exhibited weak inhibition with a very highKi/KIratio.6. The results of the study indicated that whilst thiazoles and oxazoles are unlikely to be extensively metabolized by aldehyde oxidase, they may inhibit the metabolism of substrates of the enzyme.