Methamphetamine and amphetamine were continuously administered to rats for 3 days by means of subcutaneously implanted osmotic minipumps. The total daily dose of each drug was approximately 4 mg/day. Dopamine, norepinephrine and serotonin determinations two weeks later indicated that both amphetamines produced a selective striatal dopamine depletion. Anatomical studies indicated that this depletion was associated with striatal nerve fiber degeneration. To determine whether this fiber degeneration induced by amphetamines was dopaminergic, the long-lasting dopamine depletion produced by methamphetamine was antagonized with alpha-methyl-para-tyrosine. This prevented the appearance of nerve fiber degeneration after methamphetamine. These findings suggest that amphetamines produce a long-term striatal dopamine depletion by destroying striatal dopamine nerve fibers.