The parenchymal cells of the pars intermedia (PI) and corticotrophs of the pars distalis (PD) synthesize pro-opiomelanocortin (POMC), which, through posttranslational processing, gives rise to a group of structurally related peptides, including MSHs, ACTH, CLIP, LPHs and endorphins. We investigated the control of release of these peptides using an in vitro system. We perifused either intact neurointermediate lobes (NI) or PD halves obtained from rats. Perifusion medium and tissue extracts were subjected to a battery of bioassays (BA) and radioimmunoassays (RIA) (including MSH-BA, α-MSH-RIA, ACTH-BA, ACTH-RIA, LPH-RIA) and a receptor-binding assay for morphine-like activity (MLA). The relative amounts of released peptide activities were examined under basal conditions and after challenging with synthetic ovine corticotrophin-releasing factor (CRF) and somatostatin. CRF stimulated the release of all assayed peptides from both the PD and PI in a dose-related manner. Stimulated release was immediate (within 3 min), constant, reversible and repeatable. Somatostatin (up to 100 ng/ml) did not alter basal release from either PD or PI. Somatostatin did block CRF-induced release from the PI but not from the PD. These observations support an action of both CRF and somatostatin in the control of secretion of POMC-derived peptides from the PI