An in vitro perifusion system was used to investigate immunoreactive β-endorphin (β-END-I) release from adult human hypothalami in response to dopamine (DA) and the DA receptor antagonist haloperidol (HAL). Administration of a 1 µM pulse of DA consistently elicited a mean (±SE) 88 ± 9% increase (p< 0.05, n = 5) in β-END-I release, whereas 1 µM HAL had no effect. Administration of 1 µM DA during three perifusions in which 1 µM HALwas added to the medium failed to alter basal β-END-I release. In contrast, DA did evoke an acute 230 + 31% increase (p< 0.05) in β-END-I release during three matching perifusions with medium containing the α-adrenergic antagonist phentolamine. These studies demonstrate that DA can stimulate in vitro release of β-END-I from the adult human hypothalamus by a DA receptor mediated mechanism.