Superfusion of the rat striatum with 100 microM of 1-methyl-4-phenylpyridinium (MPP+) induced a 70-fold increase in dopamine (DA) release and a decrease in the extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Pretreatment with riluzole (8 mg kg-1, i.p.), a compound that interferes with glutamatergic transmission, partially antagonized the effect of MPP+ on the release of DA, but did not change the effects of this toxin on the efflux of DOPAC and HVA. Riluzole did not affect the increase in DA release induced by MPP+ in vitro. The in vivo efficacy of riluzole on MPP(+)-induced DA release could be due to its central interference with glutamatergic transmission. Our data point to a protective role of riluzole with regard to DA release, a marker of the neuronal impairment induced by MPP+, a pro-parkinsonian neurotoxin.