Substitution of 9‐D‐Ala‐NH2for 9‐Gly‐NH2in the arginine‐vasopressin molecule (AVP) results in suppression of both pressor and antidiuretic activities, but leaves intact and augmented the ability of the analog to increase plasma levels of Factor VIII (FVIII). This change in the biological spectrum of AVP activities is also present when the N‐terminus of the analog is desaminated and when the 1–6 disulfide bridge is converted to a thioether bridge. The vasopressin receptor (VR) involved in the FVIII mobilization response appears to represent a third category of VR which is distinct from the smooth muscle VR and the antidiuretic VR in terms of conformational requirements for hormone‐receptor triggering. By comparing plasma FVIII levels in mixed venous blood after intravenous and various intra‐arterial injections, evidence was adduced that this third (hematological) category of receptor site (HF‐R) is in the central nervous system (CNS). Donor‐receiver experiments were carried out in anesthetized dogs. The donor animal was given the 9‐D‐Ala‐NH2analog of AVP (dDAlaAVP) by injection into the femoral vein and blood was withdrawn from the internal jugular vein 20 min later; then an injection of 20 ml plasma obtained from this latter sample of donor blood was injected into the femoral vein of a receiver animal. This injection elicited the largest dDAlaAVP‐induced increase in plasma FVIII level yet observed (under all experimental conditions employed to date), strongly suggesting (a) that the brain releases a hitherto unrecognized mobilizing (synthesis‐stimulating and/or releasing) factor for FVIII, (b) that the hematological factor receptor (HF‐R) at which dDAlaAVP acts may be beyond the blood brain barrier and (c) that AVP‐like molecules which act at HF‐R are humoral first messengers in their hematologic function as they are in their actions on smooth muscle and the distal nephron – but at the HF‐R, unlike at the pressor and antidiuretic receptors, these molecules function to effect the release of humoral second messengers which in turn bring about the release and/or increased synthesis of FVIII and plasminogen activator (PA). The 9‐D‐ Ala‐NH2AVP analog should offer advantage over 1‐desamino‐[8‐D‐Arg]‐VP (dDAVP) in the management of bleeding syndromes related to FVIII deficiency because