Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.