Fluoxetine injected i.p. into rats at a dose of 10 mg/kg rapidly increased serotonin concentration in microdialysis fluid from the striatum by at least 4-fold, an increase that was maintained throughout the 3 hr observation period. Dopamine concentration in the microdialysis fluid did not change. The concentration of the two dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, was not changed in the microdialysis fluid, whereas the concentration of the serotonin metabolite, 5-hydroxyindoleacetic acid, was significantly decreased after fluoxetine injection. The increased extracellular concentration of serotonin no doubt resulted from inhibition of the serotonin uptake carrier by fluoxetine, and the lack of change in dopamine is evidence for the specificity of action of this uptake inhibitor.