Adrenomedullin (AM) and corticotrophin (ACTH) are both vaso-active peptides produced by a variety of cell types including endothelial cells. Although AM and ACTH are considered to be important in the control of blood pressure and the response to stress, respectively, their role in inflammation and the immune response has not been clarified. This study shows, using a cell based ELISA, that AM and ACTH induce cell surface expression of the adhesion molecules E-selectin, VCAM-1 and ICAM-1 on human umbilical vein endothelial cells (HUVEC). Further this effect appears to be mediated in part via elevation of cAMP since both peptides elevate cAMP, the cell permeable cAMP analogue, dbcAMP, is able to mimic induction of all three cell adhesion molecules and the effect of AM and ACTH is inhibited by the adenyl cyclase inhibitor, SQ22, 536. These findings demonstrate a role for AM and ACTH in the regulation of the immune and inflammatory response.