Abstract The time—response curve of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations in the striatum of the rat were measured during apomorphine, haloperidol, morphine, oxotremorine or reserpine treatment as well as after a brain lesion. The results showed that changes in DOPAC concentrations consistently preceded changes in HVA concentrations. It was concluded that HVA must be considered as a “second metabolite” rather than as a marker of extra-neuronal metabolism. The turnover of HVA calculated after tropolone treatment revealed that this compound can be considered as a reliable COMT inhibitor. The turnover of 3-methoxytyramine (3-MT) calculated after tropolone treatment (during MAO inhibition) appeared to be 1.9 nmol/g/h. From this relatively low value it was concluded that 3-MT cannot be considered as an alternative metabolite for DA degradation during MAO inhibition. 3-MT concentrations measured after apomorphine or γ-hydroxybutyric acid treatment also suggest that 3-MT leaves the brain to only a minor extent during MAO inhibition. The effects of reserpine on pargyline-induced 3-MT concentrations indicate that there is hardly any COMT-activity in dopaminergic terminals. Evidence was provided that, at least during reserpine or pargyline treatment, dopamine leaves the brain unmetabolized or via unknown metabolic pathways.