The ability of synaptosomes, prepared from striata, to take up 3H-dopamine declined rapidly during incubation at 37 degrees C, in an oxygenated Krebs-Ringer medium with 0.1 mM ascorbic acid. Ascorbic acid was responsible for this decrease. Its effectiveness after a 60 min incubation was concentration dependent from 1 microM and virtually complete for 0.1 mM. Furthermore, a decrease of synaptosomal membrane fluidity was revealed by measurements of fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene. This decrease was potentiated by Fe2+ ions (1 microM). In contrast, it was prevented by the Fe2+ ion chelator, desferrioxamine (0.1 mM), by the Ginkgo biloba extract EGb 761 [2-16 micrograms/ml], as well as by the flavonoid quercetin (0.1 microM). This preventive effect was shared by trolox C (from 0.1 mM). It is concluded that peroxidation of neuronal membrane lipids induced by ascorbic acid/Fe2+ is associated with a decrease in membrane fluidity which, in turn, reduces the ability of the dopamine transporter to take up dopamine.