The effects of (+) and (-) 3,4-methylenedioxymethamphetamine (MDMA) and racemic p-chloroamphetamine (PCA) on extracellular dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as the metabolite of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), were determined in dialysates of the striatum conscious rats by using intracerebral dialysis and high performance liquid chromatography with electrochemical detection (HPLC-EC). The (+) and (-)MDMA isomers (5, 10 mg/kg, s.c.) and PCA (2.5, 5 mg/kg, s.c.) caused a rapid increase of extracellular levels of dopamine and decreased extracellular levels of DOPAC and HVA immediately after administration in dialysates of striatum. The order of potency for this effect was PCA greater than (+)MDMA greater than (-)MDMA. The levels of 5-HIAA also decreased after the administration of drugs, but the effect had a slower time course than DOPAC and HVA and did not exhibit an enantiomeric difference. The data indicate that, although these drugs are thought to affect the 5-HT neuronal system preferentially, they also affect dopamine systems and by a mechanism in which the (+) isomer was more potent than the (-).