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. pi-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 the pi-excessive azaheterocycles benzothiazole, 1,2-benzisoxazole, and 2-substituted benzoxazoles was characterised by a Ki/KI ratio greater than 1.0, where Ki is the inhibitor constant for binding to the free enzyme and KI is the inhibitor constant for binding to the ES complex. In contrast, five pi-deficient methyl-substituted quinolines, which are known substrates for aldehyde oxidase, exhibited a Ki/KI ratio of less than 1.0. 5. The pi-excessive heterocycles 2,3-benzthiophene and 2,3-benzfuran, which do not contain a nitrogen atom, exhibited weak inhibition with a very high Ki/KI ratio. 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.