Increased formation of hydroxyl free radicals (.OH) reflected by .OH adduct of salicylate in brain dialysate was demonstrated during the sustained (more than 2 hours) dopamine overflow elicited by 75 nmol of 1-methyl-4-phenyldihydropyridine (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+) in the rat striatum. Owing to its weak dopamine releasing action, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did not significantly increase the .OH formation. This data suggests that sustained elevation of dopamine in the extracellular fluid elicited by MPTP analogues can be auto-oxidized, which in turn leads (possibly by indirect mechanisms) to the formation of cytotoxic .OH free radicals near the nigrostriatal terminals.