In 1967 Tranzer and Thoenen (1,2) recognized that 6-hydroxydopamine has the capacity for selectively destroying adrenergic nerve terminals. Two hydroxyserotonin isomers have a similar effect on the serotonin-containing neurons (3,4,5,6). Since the discoveries of these phenomena, 6-hydroxydopamine and 5,6 and 5,7-dihydroxytryptamine have become valuable pharmacological tools in the selective degeneration of noradrenergic and respectively serotonergic nerve terminals. In low doses, 6-hydroxydopamine is taken up into adrenergic nerve terminals without producing any detectable damage, acting as a false neurotransmitter. The administration of large doses of 6-hydroxydopamine results in very long-lasting sympathomimetic effects which are accompanied by a gradual deterioration of various specific functions of the neuronal membrane of the adrenergic nerve terminal (7,8,9). Repeated administration of high doses of 6-hydroxydopamine leads to an extensive destruction of adrenergic nerve terminals in all species studied so far (10). In general, the cell bodies of adrenergic neurons seem to be very resistant to the destructive effect of 6-hydroxydopamine compared to the nerve terminals. The two dihydroxylated indoleamines, 5,6-dihydroxytryptamine and 5,7-dihydroxytryptamine, produce long-lasting depletions in brain serotonin (3,11,12). Biochemical and morphological evidence suggests that these severe reductions of serotonin level are the result of degeneration of the axons and terminals of central serotonin containing neurons (13,14,15). These neurocytotoxic agents exhibit many pharmacological and biochemical properties which are beyond the scope of this short review which aims to cover only the various approaches reported in the literature dealing with the mechanism of action of above compounds.