In this study, we compared DDAVP-triggered VWF secretion into plasma in different HPS mouse mutants with the C56BL/6J background, pa (pallid, Hps9−/−, BLOC-1 deficiency), ru (ruby eye, Hps6−/−, BLOC-2 deficiency), and ep (pale ear, Hps1−/−, BLOC-3 deficiency) and found a range of defects in the stimulated release of VWF multimers that affect both response to DDAVP treatment and hemostasis in HPS patients. The gene discussed is BLOC1S6; the disease is Hermansky-Pudlak syndrome.