Effects of methamphetamine (15 mg/kg, s.c.) on fluorescence histochemistry of dopamine nerve fibers in neostriatum, nucleus accumbens, tuberculum olfactorium and medial frontal cortex were investigated in rats treated every 6 h for 24 h and killed 6 and 11 days after treatment. In control rats occasional nerve fibers (probably nerve terminals) in the neostriatum showed some distortion and a strong formaldehyde-glyoxylic acid induced catecholamine fluorescence; 6 and 11 days after methamphetamine, the number of swollen nerve fibers showing strong fluorescence in this region was significantly increased. In nucleus accumbens, tuberculum olfactorium and medial frontal cortex, such fiber swellings were virtually absent in both controls and methamphetamine-treated rats. Multiple doses of methamphetamine might be toxic to neostriatal dopamine nerve fibers.