In this study, the accumulations of dopamine (DA) and norepinephrine (NE) were measured in the brain tissues and in the synaptic vesicle fractions prepared from whole brain of control rats and rats injected with L-DOPA. In the normal rat brain, a 3-fold increase in DA following L-DOPA administration was followed by a small, but not significant increase in vesicular DA, indicating a restricted vesicular uptake of exogenous DA. At the same time, NE in the vesicular fraction and in the whole brain tissue did not change, suggesting a possible link between DA vesicular uptake of DA and brain NE. However, in rats pretreated with alpha-methyl-p-tyrosine, which significantly (P less than 0.05) reduced DA and NE levels in brain tissues and in the synaptic vesicles, L-DOPA administration led to a significant increase in vesicular DA (P less than 0.05), suggesting that catecholamine depletion may result in greater vesicular uptake of cytoplasmic DA. The increase in vesicular DA was accompanied by increases in tissue and vesicular NE, underscoring again the existence of a link between vesicular uptake of DA and brain NE following L-DOPA administration. The results also demonstrated a large increase in 3,4-dihydroxyphenylacetic acid (DOPAC) following L-DOPA, in the brain tissues but not in the synaptic vesicle, indicating that monoamine oxidase activity is confined to the cytoplasm.