We examined the metabolism of 6-[¹⁸F]fluorodopamine, by assaying arterial plasma concentrations of radioactivity, 6-[¹⁸F]fluorodopamine, and 6-[¹⁸F]fluorodopamine metabolites in untreated subjects or subjects given desipramine to block neuronal uptake of catecholamines or tyramine to displace vesicular amines. After the 3-min 6-[¹⁸F]fluorodopamine infusion, plasma 6-[¹⁸F]fluorodopamine levels declined precipitously, total radioactivity declining slowly. After 30 min, the main identified metabolite was 6-[¹⁸F]fluorodopamine-sulfate. Desipramine attenuated the rapid increase in plasma 6-[¹⁸F]fluorodihydroxyphenylacetic acid levels, and tyramine briefly increased 6-[¹⁸F]fluorodopamine levels. Neither drug affected 6-[¹⁸F]fluorodopamine-sulfate levels. The results indicate that soon after 6-[¹⁸F]fluorodopamine infusion, plasma radioactivity corresponds mainly to 6-[¹⁸F]fluorodopamine metabolites; that sympathetic nerves rapidly remove 6-[¹⁸F]fluorodopamine, which then undergoes oxidative deamination in the neuronal cytoplasm and sequestration in sympathetic vesicles; and that sulfoconjugation of [¹⁸F]fluorodopamine occurs extraneuronally.