Du 24565, 6-nitro,2-(1-piperazinyl)quinoline, is a potent and selective inhibitor of the synaptosomal uptake of serotonin (5-HT). At concentrations at least 10(3)-fold higher it affects the uptake of norepinephrine (NA) and dopamine (DA), The IC50 values are: 5-HT: 4 x 10(-8) M; NA: 6 x 10(-5) M and DA: 4 x 10(-5) M. Uptake of 5-HT by rat blood platelets is also strongly inhibited (Ki approximately 5 x 10(-8) M); the inhibition is probably noncompetitive. In vivo, DU 24565 is active at low oral doses: the 5-HT depletion in rat brain caused by p-chloroamphetamine is antagonized by DU 24565 (oral ED50 0.7 mg/kg). The decrease in the 5-HT content caused by 4, alpha-dimethyl-m-tyramine (H 77/77) is antagonized by DU 24565 at 1 mg/kg orally, without any effect on the depletion of catecholamines. 5-HT turnover, measured by the probenecid method, is reduced by the same dose of DU 24565. Other tests confirmed the activity and selectivity of DU 24565: it potentiated the behavioural affects of the 5-HT precursor 5-hydroxytryptophan (5-HTP) in mice (ED50 1.5 mg/kg orally); it potentiated the temperature increases caused by 5-HTP in the rabbit; it had low activity or no effect at all in NA potentiation tests. This new compound is more potent and selective than the known 5-HT uptake inhibitors. It is a potential antidepressant and can be useful as a pharmacological tool to study the role of 5-HT in the central nervous system.