WE aimed to ascertain whether pyrethroid insecticides could influence the vesicular transport of the excitatory amino acid glutamate. The incubation of rat cortical synaptic vesicles with resmethrin and permethrin, consistently stimulated both ATP-dependent and -independent uptake of [3H]glutamate, while not evoking depletion of its vesicular content. Both processes were counteracted by valinomycin, a dissipator of the transmembrane potential gradient (ΔΦsv). Meanwhile, the vesicular influx of36Cl− anions was impaired by pyrethroid concentrations which did not affect the ATP-dependent uptake of [14C]methylamine, as a marker for the proton gradient (ΔpH). Thus, the stimulation of glutamate transport appeared to involve mainly the ΔΦsv. A self-attenuating effect of selected pyrethroids on putatively enhanced excitatory transmission in severe intoxication is suggested.