We now report that 6-hydroxydopamine (0.39 +/- 0.31 nanograms/mg of tissue at 2 hr) is formed in the rat caudate nucleus after a single injection of methylamphetamine (100 mg/kg). The same dose of methylamphetamine causes approximately 50% depletion of caudate dopamine 2 weeks after the injection. We suggest that the formation of 6-hydroxydopamine from endogenous dopamine is responsible for the neurotoxicity to dopamine terminals seen after methylamphetamine administration.