Although blood pressure and heart rate effects have been reported for adrenomedullin 2 (AM-2), a new member of the CGRP super-family, little information is available regarding other biological actions of systemically administered AM-2. Accordingly, we report for the first time the integrated hemodynamic, hormonal and renal actions of the AM-2 in normal conscious sheep. AM-2 induced significant reductions in mean arterial pressure (MAP, P < 0.001). This was associated with dose-dependant rises in heart rate (P < 0.001) and cardiac output (P < 0.001) and dose-dependent falls in calculated total peripheral resistance (CTPR, P < 0.001). Right atrial pressure was increased post-infusion (P = 0.026) whereas hematocrit fell post-infusion (P = 0.001). AM-2 also induced significant hormonal changes, particularly in the renin-angiotensin-aldosterone system where plasma renin activity (PRA) was significantly activated (P < 0.001) associated with a dose-dependent rise in plasma aldosterone (P < 0.001). Plasma cyclic AMP also rose in response to AM-2 (P < 0.001), as did circulating levels of the natriuretic peptides, particularly post-infusion. In conclusion, intravenous infusions of AM-2 administered to normal conscious sheep induced significant hemodynamic actions including reduced MAP and CTPR and increased heart rate and cardiac output. Concurrently, AM-2 activated plasma cyclic AMP, PRA, aldosterone and the natriuretic peptides. With the exception of actions on aldosterone, these actions are similar to those previously reported for AM. Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.