The behaviour of some beta-carboline derivatives as inhibitors of monoamine oxidase has been studied in bovine retina. Inhibition was found not to show any significant time dependence. Di- and tetrahydro-beta-carbolines were shown to behave as reversible and competitive inhibitors. In contrast, the fully unsaturated beta-carbolines harmane, harmine and harmaline, which showed deviation from linearity at high substrate concentrations, behaved as tight-binding inhibitors. In these cases, the concentration of the enzyme and the inhibitor were of the same order. This was confirmed by the Ki values for these compounds in the nanomolar concentration range. Consistent with this was that inhibition was only partly reversed by dialysis for 18 h at 4 degrees C, although complete reversal was observed after dialysis for the same period at 37 degrees C. Structure-activity relationships indicated that substitution of a methoxy group at the C7 position of the aromatic ring is determinant for this tight-binding behaviour; a substitution of this group at the C6 position greatly reduced inhibition. Since beta-carbolines have been reported to be formed endogenously, this suggests that they might have important physiological actions on monoamine oxidase activity in-vivo. In contrast, all the beta-carbolines investigated in this study had low potencies as inhibitors of monoamine oxidase B.