We investigated the ability of selective opioid agonists and antagonists to influence pro-opiomelanocortin peptide secretion from the rat neurointermediate lobe in vitro. The μ-opioid agonist DAMGO ([D-Ala2, N-Me- Phe4, Gly5-ol]enkephalin) significantly stimulated β-endorphin and α- melanocyte-stimulating hormone release relative to controls early (30 min) in the incubation period. Similar effects on β-endorphin secretion were observed with the selective μ-opioid agonist dermorphin. The δ-opioid receptor agonist DPDPE ([D-Pen2,5]enkephalin) weakly inhibited β- endorphin secretion relative to controls while the κ-opioid receptor agonist U50488 had no effect. The μ-opioid selective antagonist CTOP (D-Phe-Cys-Tyr- D-Trp-Orn-Thr-Pen-Thr-NH2) inhibited basal β-endorphin secretion while κ- and δ-opioid receptor antagonists had no effect. Our data support a role for local μ-opioid receptor control of intermediate lobe pro-opiomelanocortin peptide secretion. Peptide secretion from melanotropes appears to be tonically stimulated by activation of μ-opioid receptors in the absence of intact neuronal innervation to the intermediate lobe. (C) 2000 Harcourt Publishers Ltd.