The effects of the μ-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (μg/kg) or via a microdialysis probe placed into the ventral tegmental area or the nucleus accumbens (nmol). The effect of fentanyl given into the nucleus accumbens was blocked by systemic administration of the non-selective opioid receptor antagonist naloxone and by accumbens administration of d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH 2 (nmol), a μ-opioid receptor antagonist, and naltrindole (nmol), a non-selective δ-opioid receptor antagonist, in a dose-dependent manner. The δ 2 -opioid receptor antagonist, naltriben (nmol), also blocked the effects of fentanyl, whereas the δ 1 -opioid receptor antagonist, (E)-7-benzylidenenaltrexone (nmol), was ineffective. When marginally effective doses of d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH 2 and naltriben were given simultaneously, the effect of fentanyl was nearly fully blocked; the pretreatment itself had no effect. Administration of the μ-opioid receptor agonist [d-Ala 2 , N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (nmol), the δ 1 -opioid receptor agonist [d-Pen 2 , 5 ]-enkephalin (nmol) or the δ 2 -opioid receptor agonist [d-Ala 2 ,Glu 4 ]-deltorphin (nmol) into the nucleus accumbens enhanced the amount of accumbal dopamine. This study provides evidence that not only activation of δ 1 - and δ 2 -opioid receptors, but also activation of μ-opioid receptors in the nucleus accumbens increases the release of accumbal dopamine in freely moving rats.We suggest that the effect of intra-accumbens administration of fentanyl upon accumbal release of dopamine is either due to the simultaneous activation of μ-opioid receptors and δ 2 -opioid receptors or due to activation of μ-opioid receptors that interact with δ 2 -opioid receptors in a complex manner.