Rotigaptide (ZP-123) is a novel hexapeptide (Ac-D-Tyr-D-Pro-D-Hyp-Gly-D-Ala-Gly-NH2), originally developed as an antiarrythmic agent it has now been safely administered to healthy humans as a six day continuous infusion of up to 20 mg (0.30 mmol) per day and is now in Phase II clinical trials. It has been shown to promote electrical coupling between ventricular myocytes by increasing gap junction conductance potentially via alterations in the phosphorylation status of Cx43 and it increases the number of gap junctions in the ischaemic myocardium It potentiates gap junction-mediated dye transfer via Cx43 expressing HeLa cells but not via Cx26 or Cx32 but its effects on electrical conduction and dye transfer via Cx37 and Cx40, the other major vascular connexins, have yet to be assessed. However, we have recently shown that Cx43 is required for the mediation of EDHF vasodilatation of human subcutaneous resistance vessels.