Adrenomedullin (ADM) is a novel peptide with actions which include reduction of arterial pressure and interaction with a number of hormone systems. In order to assess possible interactions with the renin-angiotensin system (RAS) and the hypothalamo-pituitary-adrenal (HPA) axis, we have examined neurohumoral responses to hypotensive haemorrhage (15 ml/kg over 15 min) with or without co-infusions of ADM (5.5 pmol/kg per min) in six non-pregnant and eight pregnant conscious sheep. Haemorrhage induced a greater decrease in arterial pressure, but a blunted increase in heart rate in pregnant sheep. There was no significant effect of ADM on haemodynamic responses to haemorrhage in either group. In non-pregnant sheep, haemorrhage-induced activation of both RAS and HPA was significantly augmented by ADM, as indicated by greater increases in plasma renin activity (P<0.01), angiotensin II (P<0.05) and arginine vasopressin (P<0.01). In contrast, ADM did not augment these responses to haemorrhage in pregnant sheep. Rather, plasma concentrations of aldosterone (P=0.039) and adrenocorticotrophic hormone (P=0.012) were decreased by ADM. In conclusion, ADM-induced augmentation of the RAS and HPA responses to hypotensive haemorrhage is abolished in the pregnant state.