To determine whether oxygen free radicals are involved in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, the effect of dimethylthiourea (DMTU), an effective hydroxyl radical scavenger, on MPTP-induced changes of [3H]dopamine uptake was investigated in rat striatal slices. The uptake of [3H]dopamine was decreased by MPTP treatment, and DMTU prevented the MPTP-induced decrease of [3H]dopamine uptake in a dose-dependent manner. The highest dose of DMTU used in this study completely prevented the MPTP-induced decrease of [3H]dopamine uptake. These results indicate that free radicals play a major role in the pathogenetic mechanism of MPTP-induced neurotoxicity.