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The placenta has been shown to contain ACTH and β-endorphin but the roles of these peptides are unknown. To investigate whether they are released into the maternal circulation from the placenta in response to physiological stimuli the effects of hypoglycaemic stress were investigated. Plasma samples were collected from the femoral artery (FA) and uterovarian (UV) vein of nine pregnant sheep before and during hypoglycaemia induced by intravenous insulin (100U). Plasma concentrations of ovine β-endorphin (oβ-EP) were measured by radioimmunoassay. Concentrations of oβ-EP rose in both vessels by 60 min after insulin. The peak concentrations of oβ-EP (pmol/l) were 122 ± 29 (mean ± SEM, n=8) in the UV and 96±24 (n=9) fmol/ml in the FA 60 min after insulin injection. There was no difference between the concentrations of oβ-EP in the vessels before insulin injection but at 60 and 120 min after insulin the concentrations of oβ-EP were significantly higher in the UV than FA (P<0.02, analysis of variance). This indicates that the pregnant uterus or placenta can respond to hypoglycaemia by secreting β-EP into the maternal circulation. It is therefore possible that placental pro-opiomelanocortin (POMC) peptides may have a role in maternal endocrinology and metabolism.