Von Willebrand factor (VWF) and P-selectin share an identical intracellular storage compartment and transport to the cell surface. We induced degranulation of the Weibel-Palade bodies and measured circulating (c)P-selectin in plasma to test whether soluble P-selectin is present in the Weibel-Palade bodies, or if P-selectin bound to the cell membrane of endothelial cells (EC) is rapidly proteolytically cleaved in vivo. A dose of 0.3 microgram/kg of desmopressin (DDAVP) or placebo was infused over 30 min to eight healthy men in a double-blind cross-over study. Plasma levels of cP- selectin and VWF-Ag were followed for 24 h. Despite a twofold increase in VWF-Ag levels immediately after a 2 h after infusion of DDAVP, no significant change in plasma concentrations of cP-selectin were observed. In summary, degranulation of the Weibel-Palade bodies is an unlikely source of cP-selectin. Thus cP-selectin in healthy subjects is conceivably attributable to other mechanisms, such as minor degrees of platelet activation or transcription induction of an alternatively spliced P-selectin.