The effects of racemic mixtures of representative tetrahydroisoquinoline and tetrahydroprotoberberine alkaloids on the mechanisms of catecholamine uptake and retention were studied in synaptosomal preparations from whole rat brain. The synaptosomes were incubated with ( 14 C)-d,l- norepinephrine or ( 14C)-dopamine in the presence of various concentrations of salsolinol (SAL), tetrahydropapaveroline (THP), 2,3,10,11-tetrahydroxyberbine (THB), or 2,3,10,11-tetramethoxyberbine (TMB). Levels of radioactivity in synaptosomes preloaded with labeled norepinephrine were significantly diminished by the addition of 10 −4 M THP, THB or SAL to approximately 42.7 per cent (P < 0·001), 85.8 per cent (P < 0·02) and 85.9 per cent (P < 0·01), respectively, of control preparations. THP, 10 −5 M, also significantly decreased synaptosomal retention of the labeled neuroamine. ( 14C)-dopamine was used in an analysis of alkaloid effects on catecholamine uptake kinetics. K i values obtained were: 0·7 × 10 −5 M (THP); 3·5 × 10 −5 M (THB); 1·25 × 10 −4 M (SAL); and 2·2 × 10 −4 M (TMB). These results have been interpreted to suggest that the affinity of these amine-derived alkaloids for the catecholaminergic uptake mechanisms, although not marked when compared to that of dopamine or norepinephrine, may be sufficient under conditions of highly localized formation and accumulation to have important physiological sequelae.