Caffeine was chronically administered in four doses (0, 10, 25, and 50 mg/kg/day) to rats via twice-daily intraperitoneal injections for 30 days. Concentrations of brain tissue monoamines, dopamine (DA), norepinephrine (NE), and serotonin (5HT), and monoamine metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5HIAA), were determined. At the 10 mg/kg/day dose, no significant changes were found compared with controls. At 25 mg/kg/day and 50 mg/kg/day significant changes were observed within each monoamine system. In striatum, DA and 5HT were increased, while DOPAC was decreased. In frontal cortex, NE was increased. In cerebellum, 5HT and MHPG were increased.