β-Endorphin is an endogenous opioid peptide implicated in reward processes, but the brain sites directly involved in its putative role in reward have not been identified. Here we used in vivo microdialysis in rats to study the effect of a potent reinforcer, lateral hypothalamus self-stimulation (LHSS), on the extracellular levels of β-endorphin in the nucleus accumbens (NAS). The NAS is involved in the reinforcing effects of natural and artificial rewards, has high density of opioid receptors and is innervated by arcuate nucleus β-endorphin neurons. LHSS had no effect on extracellular levels of β-endorphin in the NAS. Surprisingly, extinction of the self-stimulation behaviour induced a rapid increase in NAS β-endorphin levels. In a subsequent experiment in rats previously trained to self-administer heroin for 10 days, β-endorphin levels also were increased during a test for extinction of the heroin-reinforced behaviour. Finally, the increase in extracellular β-endorphin levels in the NAS was also observed during exposure to an aversive stimulus, intermittent footshock (20 min). These results indicate a possible role for increased levels of NAS β-endorphin in the organism's adaptive response to stress and frustration.