To examine biochemical changes in the brain histamine (HA) neuron system after acute and chronic administrations of methamphetamine (MAP), HA levels and histidine decarboxylase (HDC) activities in the rat cortex, striatum, diencephalon, midbrain, pons-medulla and cerebellum were measured. In the cortex and striatum, acute administration of MAP (1 and 3 mg/kg) increased HA levels 1 h later. Acute administration of MAP (10 mg/kg) and chronic administration of MAP (3 mg/kg) for 21 days also increased HA levels and HDC activities in the cortex and striatum I h after the last injection. In the diencephalon, acute administration of MAP (3 and 10 mg/kg) and chronic administration of MAP (3 mg/kg) decreased HA level 1 h after the last injection, but chronic administration of MAP (3 mg/kg) increased HDC activity 1 h after the last injection. There were no significant changes in HA levels and HDC activities in other regions after acute and chronic administrations of MAP. These findings suggest that MAP may activate the brain HA neuron system, although MAP acts more strongly on the cortex and striatum than on the diencephalon.